rs2260160

chr15-43603445-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153700.2(STRC):c.4376-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,605,710 control chromosomes in the GnomAD database, including 27,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (8290 hom., cov: 31)
  • Exomes 𝑓: 0.13 (19452 hom.)
• Consequence: STRC NM_153700.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.584

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]

CKMT1B (HGNC:1995): (creatine kinase, mitochondrial 1B) Mitochondrial creatine (MtCK) kinase is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine. It belongs to the creatine kinase isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Many malignant cancers with poor prognosis have shown overexpression of ubiquitous mitochondrial creatine kinase; this may be related to high energy turnover and failure to eliminate cancer cells via apoptosis. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 have been identified which encode identical mitochondrial creatine kinase proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-43603445-C-T is Benign according to our data. Variant chr15-43603445-C-T is described in ClinVar as [Benign]. Clinvar id is 1275080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2	c.4376-34G>A		intron_variant		ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7	c.4376-34G>A		intron_variant		5	NM_153700.2	P2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38268 AN: 151560 Hom.: 8246 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.218

GnomAD3 exomes AF: 0.179 AC: 44337 AN: 247432 Hom.: 6265 AF XY: 0.169 AC XY: 22653 AN XY: 134076

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.333

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.0742

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.130 AC: 188328 AN: 1454032 Hom.: 19452 Cov.: 31 AF XY: 0.130 AC XY: 93970 AN XY: 723666

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0737

Gnomad4 NFE exome AF: 0.0997

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.253 AC: 38375 AN: 151678 Hom.: 8290 Cov.: 31 AF XY: 0.251 AC XY: 18587 AN XY: 74112

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.0982

Gnomad4 OTH AF: 0.221

Alfa AF: 0.138 Hom.: 2551

Bravo AF: 0.281

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.87
Dann	Benign	0.28

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: rs2260160; hg19: chr15-43895643; COSMIC: COSV55853491; COSMIC: COSV55853491;