rs2447196

chr15-43601620-G-A

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.4546-69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,536,830 control chromosomes in the GnomAD database, including 21,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (5982 hom., cov: 30)
  • Exomes 𝑓: 0.12 (15167 hom.)
• Consequence: STRC NM_153700.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.399

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=-0.7).
• BP6: Variant 15-43601620-G-A is Benign according to our data. Variant chr15-43601620-G-A is described in ClinVar as [Benign]. Clinvar id is 1282790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2	c.4546-69C>T		intron_variant		ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7	c.4546-69C>T		intron_variant		5	NM_153700.2	P2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33263 AN: 151790 Hom.: 5968 Cov.: 30

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.122 AC: 168950 AN: 1384922 Hom.: 15167 Cov.: 24 AF XY: 0.122 AC XY: 84613 AN XY: 692270

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0975

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.219 AC: 33323 AN: 151908 Hom.: 5982 Cov.: 30 AF XY: 0.216 AC XY: 16043 AN XY: 74258

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0934

Gnomad4 OTH AF: 0.198

Alfa AF: 0.123 Hom.: 2796

Bravo AF: 0.247

Asia WGS AF: 0.243 AC: 844 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	-0.70
Cadd	Benign	9.4
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: rs2447196; hg19: chr15-43893818; COSMIC: COSV55853034; COSMIC: COSV55853034;