rs41538178

chr11-69818865-C-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005247.4(FGF3):c.69G>T(p.Ala23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,460,720 control chromosomes in the GnomAD database, including 8,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (789 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7230 hom.)
• Consequence: FGF3 NM_005247.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.236

Genes affected

FGF3 (HGNC:3681): (fibroblast growth factor 3) 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. This gene was identified by its similarity with mouse fgf3/int-2, a proto-oncogene activated in virally induced mammary tumors in the mouse. Frequent amplification of this gene has been found in human tumors, which may be important for neoplastic transformation and tumor progression. Studies of the similar genes in mouse and chicken suggested the role in inner ear formation. [provided by RefSeq, Jul 2008]

LOC107984368 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 11-69818865-C-A is Benign according to our data. Variant chr11-69818865-C-A is described in ClinVar as [Benign]. Clinvar id is 259690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.236 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF3	NM_005247.4	c.69G>T	p.Ala23=	synonymous_variant	1/3	ENST00000334134.4
LOC107984368	XR_001748071.2	n.158C>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF3	ENST00000334134.4	c.69G>T	p.Ala23=	synonymous_variant	1/3	1	NM_005247.4	P1

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14943 AN: 151716 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0874

GnomAD3 exomes AF: 0.0899 AC: 6822 AN: 75870 Hom.: 395 AF XY: 0.0913 AC XY: 4024 AN XY: 44060

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.0452

Gnomad ASJ exome AF: 0.0368

Gnomad EAS exome AF: 0.0173

Gnomad SAS exome AF: 0.0956

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.0816

GnomAD4 exome AF: 0.102 AC: 133292 AN: 1308894 Hom.: 7230 Cov.: 32 AF XY: 0.102 AC XY: 65743 AN XY: 645836

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0457

Gnomad4 ASJ exome AF: 0.0415

Gnomad4 EAS exome AF: 0.0203

Gnomad4 SAS exome AF: 0.0947

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.0878

GnomAD4 genome AF: 0.0984 AC: 14946 AN: 151826 Hom.: 789 Cov.: 32 AF XY: 0.0981 AC XY: 7279 AN XY: 74224

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0865

Alfa AF: 0.109 Hom.: 121

Bravo AF: 0.0934

Asia WGS AF: 0.0540 AC: 187 AN: 3438

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 26, 2016	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.3
Dann	Benign	0.49

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: rs41538178; hg19: chr11-69633633;