17-7442647-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004112.4(FGF11):c.462C>T(p.Tyr154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 1,614,198 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (65 hom.)
• Consequence: FGF11 NM_004112.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

Genes affected

FGF11 (HGNC:3667): (fibroblast growth factor 11) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The function of this gene has not yet been determined. The expression pattern of the mouse homolog implies a role in nervous system development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-7442647-C-T is Benign according to our data. Variant chr17-7442647-C-T is described in ClinVar as [Benign]. Clinvar id is 771204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 838 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF11	NM_004112.4	c.462C>T	p.Tyr154=	synonymous_variant	4/5	ENST00000293829.9
FGF11	NM_001303460.2	c.285C>T	p.Tyr95=	synonymous_variant	4/5
FGF11	NR_130156.2	n.502C>T		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF11	ENST00000293829.9	c.462C>T	p.Tyr154=	synonymous_variant	4/5	1	NM_004112.4	P1
	ENST00000576615.1	n.69+612G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 838 AN: 152204 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00901

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00606 AC: 1525 AN: 251494 Hom.: 7 AF XY: 0.00648 AC XY: 881 AN XY: 135922

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00650

Gnomad FIN exome AF: 0.00203

Gnomad NFE exome AF: 0.00943

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00797 AC: 11650 AN: 1461876 Hom.: 65 Cov.: 34 AF XY: 0.00791 AC XY: 5751 AN XY: 727242

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.00331

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00715

Gnomad4 FIN exome AF: 0.00204

Gnomad4 NFE exome AF: 0.00914

Gnomad4 OTH exome AF: 0.00712

GnomAD4 genome AF: 0.00549 AC: 837 AN: 152322 Hom.: 10 Cov.: 32 AF XY: 0.00513 AC XY: 382 AN XY: 74480

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00766

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00901

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00695 Hom.: 4

Bravo AF: 0.00511

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	15
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 31

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

Publications

LitVar

Other links and lift over

dbSNP: rs4151130; hg19: chr17-7345966; COSMIC: COSV53440308; COSMIC: COSV53440308;