chr20-34978087-C-A

Variant names:

Variant summary

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

The NM_020884.7(MYH7B):c.82C>A(p.Pro28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,613,986 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P28S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.025 ( 159 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 156 hom. )

Consequence

MYH7B
NM_020884.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.170

Publications

8 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=0.0016455948).

BP6

Variant 20-34978087-C-A is Benign according to our data. Variant chr20-34978087-C-A is described in ClinVar as Benign. ClinVar VariationId is 777541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

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.82C>A	p.Pro28Thr	missense	Exon 5 of 45	NP_065935.4	A7E2Y1-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.82C>A	p.Pro28Thr	missense	Exon 5 of 45	ENSP00000262873.8	A7E2Y1-4
MYH7B	ENST00000888939.1		c.82C>A	p.Pro28Thr	missense	Exon 1 of 40	ENSP00000558998.1
MYH7B	ENST00000971120.1		c.82C>A	p.Pro28Thr	missense	Exon 2 of 41	ENSP00000641179.1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3794

AN:

152104

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0876

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00621

AC:

1547

AN:

249270

AF XY:

0.00501

show subpopulations

Gnomad AFR exome

AF:

0.0897

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00330

GnomAD4 exome

AF:

0.00266

AC:

3882

AN:

1461764

Hom.:

156

Cov.:

AF XY:

0.00244

AC XY:

1771

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0943

AC:

3158

AN:

33478

American (AMR)

AF:

0.00418

AC:

187

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000128

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000145

AC:

161

AN:

1111992

Other (OTH)

AF:

0.00555

AC:

335

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

204

408

612

816

1020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.0250

AC:

3806

AN:

152222

Hom.:

159

Cov.:

AF XY:

0.0242

AC XY:

1798

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0876

AC:

3638

AN:

41514

American (AMR)

AF:

0.00785

AC:

120

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68022

Other (OTH)

AF:

0.0109

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.00507

Hom.:

Bravo

AF:

0.0285

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0803

AC:

348

ESP6500EA

AF:

0.000469

AC:

ExAC

AF:

0.00760

AC:

921

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.95

PhyloP100

0.17

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.22

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0090

Vest4

0.16

MVP

0.25

MPC

0.18

ClinPred

0.053

GERP RS

0.38

PromoterAI

0.062

Neutral

(source)

Varity_R

0.094

gMVP

0.35

Mutation Taster

=97/3

polymorphism (auto)

(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