rs61749187

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001250
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.324

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF3	NM_005247.4	c.325-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000334134.4	NP_005238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF3	ENST00000334134.4	c.325-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005247.4	ENSP00000334122	P1
FGF3	ENST00000646078.1	n.172-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.0247 AC: 5460 AN: 220972 Hom.: 94 AF XY: 0.0261 AC XY: 3120 AN XY: 119580

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 SAS exome AF: 0.0296

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

Gnomad4 AFR exome AF: 0.00431

Gnomad4 AMR exome AF: 0.0179

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0300

Gnomad4 FIN exome AF: 0.0225

Gnomad4 NFE exome AF: 0.0357

Gnomad4 OTH exome AF: 0.0299

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

Gnomad4 AFR AF: 0.00683

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0248

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0303 Hom.: 32

Bravo AF: 0.0231

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 10, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs61749187; hg19: chr11-69625473;