rs13317

Variant names:

• chr8-38411996-T-C
• rs13317
• NM_023110.3:c.*1632A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_023110.3(FGFR1):​c.*1632A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 230,686 control chromosomes in the GnomAD database, including 6,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4142 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2427 hom.)
• Consequence: FGFR1 NM_023110.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0420
• Publications: 67 publications found

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: G2P, Ambry Genetics, Orphanet, ClinGen
• hypogonadotropic hypogonadism 2 with or without anosmia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• osteoglophonic dysplasia

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp, Orphanet
• Pfeiffer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Pfeiffer syndrome type 1

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• 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

LOC102723716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-38411996-T-C is Benign according to our data. Variant chr8-38411996-T-C is described in ClinVar as Benign. ClinVar VariationId is 362864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023110.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1	NM_023110.3	MANE Select	c.*1632A>G		3_prime_UTR	Exon 18 of 18	NP_075598.2	P11362-1
	FGFR1	NM_001174067.2		c.*1632A>G		3_prime_UTR	Exon 19 of 19	NP_001167538.1	P11362-21
	FGFR1	NM_001354367.2		c.*393A>G		3_prime_UTR	Exon 18 of 18	NP_001341296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1	ENST00000447712.7	TSL:1 MANE Select	c.*1632A>G		3_prime_UTR	Exon 18 of 18	ENSP00000400162.2	P11362-1
	FGFR1	ENST00000425967.8	TSL:1	c.*393A>G		3_prime_UTR	Exon 18 of 18	ENSP00000393312.4	A0A8I3B1S4
	FGFR1	ENST00000397091.9	TSL:1	c.*1632A>G		3_prime_UTR	Exon 18 of 18	ENSP00000380280.5	P11362-7

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34376 AN: 152006 Hom.: 4128 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.245 AC: 19248 AN: 78562 Hom.: 2427 Cov.: 0 AF XY: 0.242 AC XY: 8805 AN XY: 36346

African (AFR) AF: 0.212 AC: 787 AN: 3710

American (AMR) AF: 0.257 AC: 614 AN: 2386

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 736 AN: 4930

East Asian (EAS) AF: 0.358 AC: 3950 AN: 11024

South Asian (SAS) AF: 0.100 AC: 68 AN: 678

European-Finnish (FIN) AF: 0.154 AC: 45 AN: 292

Middle Eastern (MID) AF: 0.190 AC: 91 AN: 480

European-Non Finnish (NFE) AF: 0.237 AC: 11497 AN: 48534

Other (OTH) AF: 0.224 AC: 1460 AN: 6528

GnomAD4 genome AF: 0.226 AC: 34431 AN: 152124 Hom.: 4142 Cov.: 32 AF XY: 0.221 AC XY: 16468 AN XY: 74364

African (AFR) AF: 0.214 AC: 8881 AN: 41500

American (AMR) AF: 0.261 AC: 3990 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 498 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1764 AN: 5166

South Asian (SAS) AF: 0.110 AC: 531 AN: 4822

European-Finnish (FIN) AF: 0.193 AC: 2041 AN: 10580

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15835 AN: 67980

Other (OTH) AF: 0.232 AC: 489 AN: 2110

Alfa AF: 0.229 Hom.: 6730

Bravo AF: 0.238

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Craniosynostosis syndrome (1)
-	-	1	Hypogonadotropic hypogonadism 2 with or without anosmia (1)
-	-	1	not provided (1)
-	-	1	Osteoglophonic dysplasia (1)
-	-	1	Trigonocephaly 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13317; hg19: chr8-38269514;