14-23412834-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000257.4(MYH7):​c.*20G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00653 in 1,613,934 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0067 ( 43 hom. )

Consequence

MYH7
NM_000257.4 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.221
Variant links:
Genes affected
MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

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=-0.59).
BP6
Variant 14-23412834-C-T is Benign according to our data. Variant chr14-23412834-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 188649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23412834-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00453 (690/152334) while in subpopulation NFE AF= 0.0077 (524/68030). AF 95% confidence interval is 0.00716. There are 3 homozygotes in gnomad4. There are 315 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH7NM_000257.4 linkc.*20G>A 3_prime_UTR_variant Exon 40 of 40 ENST00000355349.4 NP_000248.2 P12883
MYH7NM_001407004.1 linkc.*20G>A 3_prime_UTR_variant Exon 39 of 39 NP_001393933.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH7ENST00000355349 linkc.*20G>A 3_prime_UTR_variant Exon 40 of 40 1 NM_000257.4 ENSP00000347507.3 P12883

Frequencies

GnomAD3 genomes
AF:
0.00453
AC:
690
AN:
152216
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00152
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00262
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00339
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00770
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00467
AC:
1173
AN:
251314
Hom.:
3
AF XY:
0.00458
AC XY:
622
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00123
Gnomad AMR exome
AF:
0.00205
Gnomad ASJ exome
AF:
0.00159
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000882
Gnomad FIN exome
AF:
0.00333
Gnomad NFE exome
AF:
0.00823
Gnomad OTH exome
AF:
0.00505
GnomAD4 exome
AF:
0.00674
AC:
9846
AN:
1461600
Hom.:
43
Cov.:
31
AF XY:
0.00664
AC XY:
4831
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.00114
Gnomad4 AMR exome
AF:
0.00190
Gnomad4 ASJ exome
AF:
0.00126
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000951
Gnomad4 FIN exome
AF:
0.00437
Gnomad4 NFE exome
AF:
0.00816
Gnomad4 OTH exome
AF:
0.00497
GnomAD4 genome
AF:
0.00453
AC:
690
AN:
152334
Hom.:
3
Cov.:
33
AF XY:
0.00423
AC XY:
315
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.00152
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00339
Gnomad4 NFE
AF:
0.00770
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00471
Hom.:
0
Bravo
AF:
0.00422

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Scapuloperoneal myopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Myosin storage myopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

MYH7-related skeletal myopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dilated Cardiomyopathy, Dominant Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:1
Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Left ventricular noncompaction cardiomyopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy 1 Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
9.1
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

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

Other links and lift over

dbSNP: rs45548631; hg19: chr14-23882043; API