rs61749187

Variant names:

• chr11-69810705-G-A
• rs61749187
• NM_005247.4:c.325-5C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-69810705-G-A
• chr11-69810705-G-C
• chr11-69810705-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005247.4(FGF3):​c.325-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 1,572,718 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (52 hom., cov: 33)
  • Exomes 𝑓: 0.032 (856 hom.)
• Consequence: FGF3 NM_005247.4 splice_region, intron
• Scores: Splicing: ADA: 0.001250
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.324
• Publications: 2 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: ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-69810705-G-A is Benign according to our data. Variant chr11-69810705-G-A is described in ClinVar as Benign. ClinVar VariationId is 259687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0244 (3723/152352) while in subpopulation NFE AF = 0.0358 (2432/68026). AF 95% confidence interval is 0.0346. There are 52 homozygotes in GnomAd4. There are 1767 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF3	NM_005247.4	MANE Select	c.325-5C>T		splice_region intron	N/A	NP_005238.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF3	ENST00000334134.4	TSL:1 MANE Select	c.325-5C>T		splice_region intron	N/A	ENSP00000334122.2
	FGF3	ENST00000646078.1		n.172-5C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3722 AN: 152234 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.00685

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0247 AC: 5460 AN: 220972 AF XY: 0.0261

Gnomad AFR exome AF: 0.00535

Gnomad AMR exome AF: 0.0173

Gnomad ASJ exome AF: 0.0373

Gnomad EAS exome AF: 0.0000573

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.0329

Gnomad OTH exome AF: 0.0249

GnomAD4 exome AF: 0.0324 AC: 46069 AN: 1420366 Hom.: 856 Cov.: 32 AF XY: 0.0325 AC XY: 22751 AN XY: 700792

African (AFR) AF: 0.00431 AC: 140 AN: 32520

American (AMR) AF: 0.0179 AC: 737 AN: 41264

Ashkenazi Jewish (ASJ) AF: 0.0385 AC: 922 AN: 23938

East Asian (EAS) AF: 0.00 AC: 0 AN: 38960

South Asian (SAS) AF: 0.0300 AC: 2423 AN: 80882

European-Finnish (FIN) AF: 0.0225 AC: 1148 AN: 50986

Middle Eastern (MID) AF: 0.0289 AC: 161 AN: 5580

European-Non Finnish (NFE) AF: 0.0357 AC: 38787 AN: 1087752

Other (OTH) AF: 0.0299 AC: 1751 AN: 58484

GnomAD4 genome AF: 0.0244 AC: 3723 AN: 152352 Hom.: 52 Cov.: 33 AF XY: 0.0237 AC XY: 1767 AN XY: 74500

African (AFR) AF: 0.00683 AC: 284 AN: 41590

American (AMR) AF: 0.0248 AC: 380 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0248 AC: 120 AN: 4830

European-Finnish (FIN) AF: 0.0239 AC: 254 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0358 AC: 2432 AN: 68026

Other (OTH) AF: 0.0289 AC: 61 AN: 2112

Alfa AF: 0.0289 Hom.: 47

Bravo AF: 0.0231

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.76
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.0040
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: rs61749187; hg19: chr11-69625473;