Variant 8-38415024-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_023110.3(FGFR1):c.1855-123G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 730,200 control chromosomes in the GnomAD database, including 15,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3241 hom., cov: 32)

Exomes 𝑓: 0.20 ( 12755 hom. )

Consequence

FGFR1
NM_023110.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.167

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-38415024-C-G is Benign according to our data. Variant chr8-38415024-C-G is described in ClinVar as [Benign]. Clinvar id is 1292696.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR1	NM_023110.3 linkuse as main transcript	c.1855-123G>C		intron_variant		ENST00000447712.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR1	ENST00000447712.7 linkuse as main transcript	c.1855-123G>C		intron_variant		1	NM_023110.3	P4	P11362-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30336

AN:

151954

Hom.:

3232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.203

AC:

117351

AN:

578128

Hom.:

12755

AF XY:

0.198

AC XY:

60163

AN XY:

303374

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.200

AC:

30376

AN:

152072

Hom.:

3241

Cov.:

AF XY:

0.195

AC XY:

14524

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.0566

Hom.:

Bravo

AF:

0.208

Asia WGS

AF:

0.195

AC:

679

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.1

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over