rs45468101

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000257.4(MYH7):c.5284-45G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,614,246 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 43 hom., cov: 32)

Exomes 𝑓: 0.012 ( 366 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.20

Publications

2 publications found

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]

MYH7 links:

ENSG00000258444 (HGNC:):

ENSG00000258444 links:

MHRT (HGNC:51291): (myosin heavy chain associated RNA transcript) This gene encodes a spliced long non-coding RNA that may act as a cardioprotective agent in the heart. Based on a study of a similar gene in mouse, the encoded transcript may regulate chromatin remodeling by acting as a decoy to the BRG1 chromatin repressor complex thus preventing it from binding to its genomic targets. Blocking the actions of BRG1 could be crucial in protecting the heart from pathological hypertrophy. [provided by RefSeq, Dec 2014]

MHRT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 14-23415315-C-A is Benign according to our data. Variant chr14-23415315-C-A is described in ClinVar as Benign. ClinVar VariationId is 188643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000257.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH7	NM_000257.4	MANE Select	c.5284-45G>T	intron	N/A	NP_000248.2	P12883
MYH7	NM_001407004.1		c.5284-45G>T	intron	N/A	NP_001393933.1	P12883
MHRT	NR_126491.1		n.-135C>A	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH7	ENST00000355349.4	TSL:1 MANE Select	c.5284-45G>T	intron	N/A	ENSP00000347507.3	P12883
MYH7	ENST00000858540.1		c.5329-45G>T	intron	N/A	ENSP00000528599.1
MYH7	ENST00000965955.1		c.5329-45G>T	intron	N/A	ENSP00000636014.1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2236

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.0758

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.00677

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.00894

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0218

AC:

5492

AN:

251484

AF XY:

0.0217

show subpopulations

Gnomad AFR exome

AF:

0.00910

Gnomad AMR exome

AF:

0.0360

Gnomad ASJ exome

AF:

0.0305

Gnomad EAS exome

AF:

0.0759

Gnomad FIN exome

AF:

0.00707

Gnomad NFE exome

AF:

0.00948

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0125

AC:

18271

AN:

1461892

Hom.:

366

Cov.:

AF XY:

0.0132

AC XY:

9601

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00995

AC:

333

AN:

33480

American (AMR)

AF:

0.0347

AC:

1551

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0335

AC:

875

AN:

26136

East Asian (EAS)

AF:

0.0819

AC:

3251

AN:

39700

South Asian (SAS)

AF:

0.0315

AC:

2718

AN:

86258

European-Finnish (FIN)

AF:

0.00659

AC:

352

AN:

53418

Middle Eastern (MID)

AF:

0.0598

AC:

345

AN:

5768

European-Non Finnish (NFE)

AF:

0.00698

AC:

7757

AN:

1112012

Other (OTH)

AF:

0.0180

AC:

1089

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1425

2850

4275

5700

7125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0148

AC:

2256

AN:

152354

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1177

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00993

AC:

413

AN:

41588

American (AMR)

AF:

0.0241

AC:

369

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3472

East Asian (EAS)

AF:

0.0760

AC:

393

AN:

5170

South Asian (SAS)

AF:

0.0360

AC:

174

AN:

4828

European-Finnish (FIN)

AF:

0.00677

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00894

AC:

608

AN:

68038

Other (OTH)

AF:

0.0383

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

105

211

316

422

527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.0170

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.34

(source)

DANN

Benign

0.53

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over