rs2467437

Positions:

• chr15-43608777-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_153700.2(STRC):​c.3557+499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 138,384 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0045 (4 hom., cov: 26)
• Consequence: STRC NM_153700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.842

Genes affected

STRC (HGNC:16035): (stereocilin) This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]

STRC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00452 (625/138384) while in subpopulation AFR AF= 0.0146 (492/33658). AF 95% confidence interval is 0.0136. There are 4 homozygotes in gnomad4. There are 310 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRC	NM_153700.2	c.3557+499C>T		intron_variant		ENST00000450892.7	NP_714544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7	c.3557+499C>T		intron_variant		5	NM_153700.2	ENSP00000401513.2

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 621 AN: 138316 Hom.: 4 Cov.: 26

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00825

Gnomad AMR AF: 0.00248

Gnomad ASJ AF: 0.00338

Gnomad EAS AF: 0.00523

Gnomad SAS AF: 0.00181

Gnomad FIN AF: 0.000199

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.000547

Gnomad OTH AF: 0.00523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00452 AC: 625 AN: 138384 Hom.: 4 Cov.: 26 AF XY: 0.00461 AC XY: 310 AN XY: 67300

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00338

Gnomad4 EAS AF: 0.00525

Gnomad4 SAS AF: 0.00182

Gnomad4 FIN AF: 0.000199

Gnomad4 NFE AF: 0.000547

Gnomad4 OTH AF: 0.00519

Alfa AF: 0.0191 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.4
DANN	Benign	0.77

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: rs2467437; hg19: chr15-43900975; COSMIC: COSV68660367; COSMIC: COSV68660367;