chr8-38424140-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000255201 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR1	NM_023110.3	c.936+369C>T		intron_variant	Intron 7 of 17	ENST00000447712.7	NP_075598.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR1	ENST00000447712.7	c.936+369C>T		intron_variant	Intron 7 of 17	1	NM_023110.3	ENSP00000400162.2
FGFR1	ENST00000397091.9	c.930+369C>T		intron_variant	Intron 7 of 17	1		ENSP00000380280.5
FGFR1	ENST00000397108.8	c.930+369C>T		intron_variant	Intron 8 of 18	1		ENSP00000380297.4
FGFR1	ENST00000397113.6	c.930+369C>T		intron_variant	Intron 7 of 17	2		ENSP00000380302.2
FGFR1	ENST00000356207.9	c.669+369C>T		intron_variant	Intron 6 of 16	1		ENSP00000348537.5
FGFR1	ENST00000397103.5	c.663+369C>T		intron_variant	Intron 5 of 15	5		ENSP00000380292.1
FGFR1	ENST00000326324.10	c.663+369C>T		intron_variant	Intron 6 of 16	1		ENSP00000327229.6
FGFR1	ENST00000487647.5	n.*627+369C>T		intron_variant	Intron 6 of 11	1		ENSP00000435254.1

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

Gnomad4 AFR exome AF: 0.0983

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.207

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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.201

Alfa AF: 0.223 Hom.: 3838

Bravo AF: 0.197

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs3925; hg19: chr8-38281658; COSMIC: COSV58331572; COSMIC: COSV58331572;