rs2447196

Variant names:

• chr15-43601620-G-A
• rs2447196
• NM_153700.2:c.4546-69C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.399
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1282790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
STRC	NM_153700.2	c.4546-69C>T		intron_variant	Intron 23 of 28	ENST00000450892.7	NP_714544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7	c.4546-69C>T		intron_variant	Intron 23 of 28	5	NM_153700.2	ENSP00000401513.2

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

African (AFR) AF: 0.509 AC: 16405 AN: 32222

American (AMR) AF: 0.200 AC: 8671 AN: 43248

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4860 AN: 25582

East Asian (EAS) AF: 0.277 AC: 10833 AN: 39132

South Asian (SAS) AF: 0.179 AC: 15020 AN: 84048

European-Finnish (FIN) AF: 0.0405 AC: 2133 AN: 52654

Middle Eastern (MID) AF: 0.136 AC: 770 AN: 5646

European-Non Finnish (NFE) AF: 0.0975 AC: 101796 AN: 1044520

Other (OTH) AF: 0.146 AC: 8462 AN: 57870

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

African (AFR) AF: 0.483 AC: 19975 AN: 41362

American (AMR) AF: 0.196 AC: 2999 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1430 AN: 5168

South Asian (SAS) AF: 0.197 AC: 945 AN: 4802

European-Finnish (FIN) AF: 0.0399 AC: 422 AN: 10574

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0934 AC: 6348 AN: 67946

Other (OTH) AF: 0.198 AC: 418 AN: 2106

Alfa AF: 0.146 Hom.: 6537

Bravo AF: 0.247

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.4
DANN	Benign	0.77
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2447196; hg19: chr15-43893818; COSMIC: COSV55853034; COSMIC: COSV55853034;