chr20-34977663-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020884.7(MYH7B):c.-90C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,576,972 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00061 ( 8 hom. )

Consequence

MYH7B
NM_020884.7 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.343

Publications

3 publications found

Variant links:

Genes affected

MYH7B (HGNC:15906): (myosin heavy chain 7B) The myosin II molecule is a multi-subunit complex consisting of two heavy chains and four light chains. This gene encodes a heavy chain of myosin II, which is a member of the motor-domain superfamily. The heavy chain includes a globular motor domain, which catalyzes ATP hydrolysis and interacts with actin, and a tail domain in which heptad repeat sequences promote dimerization by interacting to form a rod-like alpha-helical coiled coil. This heavy chain subunit is a slow-twitch myosin. Alternatively spliced transcript variants have been found, but the full-length nature of these variants is not determined. [provided by RefSeq, Mar 2010]

MYH7B Gene-Disease associations (from GenCC):

left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH7B 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 (MetaRNN=0.006734729).

BP6

Variant 20-34977663-C-T is Benign according to our data. Variant chr20-34977663-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 737406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000903 (136/150536) while in subpopulation SAS AF = 0.00298 (14/4694). AF 95% confidence interval is 0.0018. There are 0 homozygotes in GnomAd4. There are 67 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 136 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020884.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	NM_020884.7	MANE Select	c.-90C>T		5_prime_UTR	Exon 4 of 45	NP_065935.4	A7E2Y1-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.-90C>T	5_prime_UTR	Exon 4 of 45	ENSP00000262873.8	A7E2Y1-4
MYH7B	ENST00000971120.1		c.-28C>T	5_prime_UTR	Exon 1 of 41	ENSP00000641179.1
MYH7B	ENST00000673749.1		n.445C>T	non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes

AF:

0.000904

AC:

136

AN:

150404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00113

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00298

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000384

Gnomad OTH

AF:

0.000970

GnomAD2 exomes

AF:

0.00123

AC:

250

AN:

202672

AF XY:

0.00136

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.000612

AC:

873

AN:

1426436

Hom.:

Cov.:

AF XY:

0.000683

AC XY:

482

AN XY:

705988

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

33032

American (AMR)

AF:

0.00152

AC:

AN:

39410

Ashkenazi Jewish (ASJ)

AF:

0.00214

AC:

AN:

25248

East Asian (EAS)

AF:

0.00

AC:

AN:

38398

South Asian (SAS)

AF:

0.00363

AC:

296

AN:

81490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50858

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.000259

AC:

283

AN:

1093354

Other (OTH)

AF:

0.000967

AC:

AN:

58938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000903

AC:

136

AN:

150536

Hom.:

Cov.:

AF XY:

0.000912

AC XY:

AN XY:

73502

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

41044

American (AMR)

AF:

0.00112

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5022

South Asian (SAS)

AF:

0.00298

AC:

AN:

4694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000384

AC:

AN:

67652

Other (OTH)

AF:

0.000960

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000858

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.00225

AC:

ESP6500EA

AF:

0.000480

AC:

ExAC

AF:

0.00115

AC:

137

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

MYH7B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.014

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.42

PhyloP100

0.34

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.080

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Vest4

0.20

MVP

0.56

MPC

0.52

ClinPred

0.047

GERP RS

1.4

PromoterAI

0.067

Neutral

(source)

Varity_R

0.081

gMVP

0.55

Mutation Taster

=91/9

polymorphism

(source)

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

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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