Variant rs2260160 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.584

Variant links:

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 links:

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]

CKMT1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.4376-34G>A		intron_variant		ENST00000450892.7	NP_714544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 linkuse as main transcript	c.4376-34G>A		intron_variant		5	NM_153700.2	ENSP00000401513	P2

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38268

AN:

151560

Hom.:

8246

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.130

AC XY:

93970

AN XY:

723666

show subpopulations

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.:

AF XY:

0.251

AC XY:

18587

AN XY:

74112

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over