chr8-38428707-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000526570.5(FGFR1):n.2114C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 489,844 control chromosomes in the GnomAD database, including 11,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2854 hom., cov: 32)

Exomes 𝑓: 0.21 ( 8289 hom. )

Consequence

FGFR1
ENST00000526570.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.533

Publications

27 publications found

Variant links:

Genes affected

FGFR1 (HGNC:3688): (fibroblast growth factor receptor 1) The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

FGFR1 Gene-Disease associations (from GenCC):

encephalocraniocutaneous lipomatosis
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Hartsfield-Bixler-Demyer syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, ClinGen
hypogonadotropic hypogonadism 2 with or without anosmia
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
osteoglophonic dysplasia
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Pfeiffer syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Pfeiffer syndrome type 1
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Jackson-Weiss syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated trigonocephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
septooptic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
holoprosencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FGFR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-38428707-G-A is Benign according to our data. Variant chr8-38428707-G-A is described in ClinVar as Benign. ClinVar VariationId is 1231058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR1	NM_023110.3 link	c.359-272C>T		intron_variant	Intron 3 of 17	ENST00000447712.7	NP_075598.2	P11362-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGFR1	ENST00000447712.7 link	c.359-272C>T	intron_variant	Intron 3 of 17	1	NM_023110.3	ENSP00000400162.2	P11362-1
FGFR1	ENST00000397091.9 link	c.359-272C>T	intron_variant	Intron 3 of 17	1		ENSP00000380280.5	P11362-7
FGFR1	ENST00000397108.8 link	c.359-272C>T	intron_variant	Intron 4 of 18	1		ENSP00000380297.4	P11362-7
FGFR1	ENST00000397113.6 link	c.359-272C>T	intron_variant	Intron 3 of 17	2		ENSP00000380302.2	P11362-7
FGFR1	ENST00000356207.9 link	c.92-272C>T	intron_variant	Intron 2 of 16	1		ENSP00000348537.5	P11362-3
FGFR1	ENST00000397103.5 link	c.92-272C>T	intron_variant	Intron 1 of 15	5		ENSP00000380292.1	E7EU09
FGFR1	ENST00000326324.10 link	c.92-272C>T	intron_variant	Intron 2 of 16	1		ENSP00000327229.6	P11362-14
FGFR1	ENST00000487647.5 link	n.*50-272C>T	intron_variant	Intron 2 of 11	1		ENSP00000435254.1	E9PKX3

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25894

AN:

152054

Hom.:

2850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.0949

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.211

AC:

71315

AN:

337672

Hom.:

8289

Cov.:

AF XY:

0.211

AC XY:

37610

AN XY:

178082

show subpopulations

African (AFR)

AF:

0.0378

AC:

376

AN:

9952

American (AMR)

AF:

0.332

AC:

4859

AN:

14640

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

3093

AN:

10374

East Asian (EAS)

AF:

0.0846

AC:

1881

AN:

22238

South Asian (SAS)

AF:

0.217

AC:

9186

AN:

42246

European-Finnish (FIN)

AF:

0.211

AC:

3935

AN:

18690

Middle Eastern (MID)

AF:

0.232

AC:

338

AN:

1454

European-Non Finnish (NFE)

AF:

0.219

AC:

43412

AN:

198624

Other (OTH)

AF:

0.218

AC:

4235

AN:

19454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2632

5265

7897

10530

13162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.170

AC:

25901

AN:

152172

Hom.:

2854

Cov.:

AF XY:

0.173

AC XY:

12855

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0424

AC:

1761

AN:

41526

American (AMR)

AF:

0.276

AC:

4216

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1094

AN:

3472

East Asian (EAS)

AF:

0.0949

AC:

491

AN:

5174

South Asian (SAS)

AF:

0.215

AC:

1036

AN:

4820

European-Finnish (FIN)

AF:

0.199

AC:

2112

AN:

10600

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14613

AN:

67982

Other (OTH)

AF:

0.189

AC:

398

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1055

2110

3164

4219

5274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.214

Hom.:

7681

Bravo

AF:

0.174

Asia WGS

AF:

0.160

AC:

562

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.7

(source)

DANN

Benign

0.70

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over