chr11-69818865-C-A

Variant names:

• chr11-69818865-C-A
• rs41538178
• NM_005247.4:c.69G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005247.4(FGF3):​c.69G>T​(p.Ala23Ala) 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:5
• Conservation: PhyloP100: -0.236
• Publications: 6 publications found

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]

FGF3 Gene-Disease associations (from GenCC):

• deafness with labyrinthine aplasia, microtia, and microdontia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

LOC107984368 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005247.4. 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
	FGF3	NM_005247.4	MANE Select	c.69G>T	p.Ala23Ala	synonymous	Exon 1 of 3	NP_005238.1	P11487

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF3	ENST00000334134.4	TSL:1 MANE Select	c.69G>T	p.Ala23Ala	synonymous	Exon 1 of 3	ENSP00000334122.2	P11487
	ENSG00000300527	ENST00000772585.1		n.-106C>A		upstream_gene	N/A

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

GnomAD2 exomes AF: 0.0899 AC: 6822 AN: 75870 AF XY: 0.0913

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 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

African (AFR) AF: 0.119 AC: 3096 AN: 26114

American (AMR) AF: 0.0457 AC: 1092 AN: 23892

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 936 AN: 22546

East Asian (EAS) AF: 0.0203 AC: 579 AN: 28502

South Asian (SAS) AF: 0.0947 AC: 6760 AN: 71354

European-Finnish (FIN) AF: 0.121 AC: 4029 AN: 33278

Middle Eastern (MID) AF: 0.0465 AC: 182 AN: 3912

European-Non Finnish (NFE) AF: 0.107 AC: 111882 AN: 1045348

Other (OTH) AF: 0.0878 AC: 4736 AN: 53948

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

African (AFR) AF: 0.115 AC: 4763 AN: 41450

American (AMR) AF: 0.0513 AC: 783 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 140 AN: 3468

East Asian (EAS) AF: 0.0158 AC: 81 AN: 5118

South Asian (SAS) AF: 0.0909 AC: 439 AN: 4832

European-Finnish (FIN) AF: 0.109 AC: 1149 AN: 10514

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7324 AN: 67882

Other (OTH) AF: 0.0865 AC: 182 AN: 2104

Alfa AF: 0.109 Hom.: 121

Bravo AF: 0.0934

Asia WGS AF: 0.0540 AC: 187 AN: 3438

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.3
DANN	Benign	0.49
PhyloP100		-0.24
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: rs41538178; hg19: chr11-69633633;