rs3925

Variant names:

• chr8-38424140-G-A
• rs3925
• NM_023110.3:c.936+369C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-38424140-G-A
• chr8-38424140-G-C
• chr8-38424140-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023110.3(FGFR1):​c.936+369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 397,934 control chromosomes in the GnomAD database, including 8,798 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3211 hom., cov: 32)
  • Exomes 𝑓: 0.20 (5587 hom.)
• Consequence: FGFR1 NM_023110.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629
• Publications: 26 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

ENSG00000255201 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 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.936+369C>T		intron	N/A	NP_075598.2	P11362-1
	FGFR1	NM_001174067.2		c.1029+369C>T		intron	N/A	NP_001167538.1	P11362-21
	FGFR1	NM_001354367.2		c.930+369C>T		intron	N/A	NP_001341296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1	ENST00000447712.7	TSL:1 MANE Select	c.936+369C>T		intron	N/A	ENSP00000400162.2	P11362-1
	FGFR1	ENST00000425967.8	TSL:1	c.930+369C>T		intron	N/A	ENSP00000393312.4	A0A8I3B1S4
	FGFR1	ENST00000397091.9	TSL:1	c.930+369C>T		intron	N/A	ENSP00000380280.5	P11362-7

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28952 AN: 151966 Hom.: 3204 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.204 AC: 50274 AN: 245850 Hom.: 5587 Cov.: 0 AF XY: 0.196 AC XY: 25871 AN XY: 132072

African (AFR) AF: 0.0983 AC: 708 AN: 7204

American (AMR) AF: 0.222 AC: 2676 AN: 12072

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 1010 AN: 6536

East Asian (EAS) AF: 0.323 AC: 4085 AN: 12638

South Asian (SAS) AF: 0.113 AC: 4575 AN: 40452

European-Finnish (FIN) AF: 0.182 AC: 2647 AN: 14566

Middle Eastern (MID) AF: 0.203 AC: 474 AN: 2330

European-Non Finnish (NFE) AF: 0.229 AC: 31422 AN: 137112

Other (OTH) AF: 0.207 AC: 2677 AN: 12940

GnomAD4 genome AF: 0.191 AC: 28976 AN: 152084 Hom.: 3211 Cov.: 32 AF XY: 0.187 AC XY: 13871 AN XY: 74346

African (AFR) AF: 0.102 AC: 4221 AN: 41490

American (AMR) AF: 0.224 AC: 3428 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1625 AN: 5162

South Asian (SAS) AF: 0.103 AC: 498 AN: 4822

European-Finnish (FIN) AF: 0.186 AC: 1965 AN: 10570

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

European-Non Finnish (NFE) AF: 0.234 AC: 15876 AN: 67980

Other (OTH) AF: 0.201 AC: 422 AN: 2102

Alfa AF: 0.218 Hom.: 10463

Bravo AF: 0.197

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.71
PhyloP100		0.63
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: rs3925; hg19: chr8-38281658; COSMIC: COSV58331572; COSMIC: COSV58331572;