20-34977669-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_020884.7(MYH7B):c.-84C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,376,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

MYH7B
NM_020884.7 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.202

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09736079).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000104 (13/125490) while in subpopulation AMR AF = 0.000675 (7/10364). AF 95% confidence interval is 0.000316. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 13 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.-84C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 45	NP_065935.4	A7E2Y1-4
	MYH7B	NM_020884.7	MANE Select	c.-84C>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.-84C>T	5_prime_UTR_premature_start_codon_gain	Exon 4 of 45	ENSP00000262873.8	A7E2Y1-4
MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.-84C>T	5_prime_UTR	Exon 4 of 45	ENSP00000262873.8	A7E2Y1-4
MYH7B	ENST00000971120.1		c.-22C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 41	ENSP00000641179.1

Frequencies

GnomAD3 genomes

AF:

0.000104

AC:

AN:

125490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000675

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000503

AC:

AN:

198716

AF XY:

0.0000659

show subpopulations

Gnomad AFR exome

AF:

0.0000869

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000168

AC:

AN:

1250746

Hom.:

Cov.:

AF XY:

0.0000227

AC XY:

AN XY:

616830

show subpopulations

African (AFR)

AF:

0.000107

AC:

AN:

27912

American (AMR)

AF:

0.000267

AC:

AN:

33676

Ashkenazi Jewish (ASJ)

AF:

0.0000533

AC:

AN:

18760

East Asian (EAS)

AF:

0.00

AC:

AN:

20918

South Asian (SAS)

AF:

0.00

AC:

AN:

79846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4786

European-Non Finnish (NFE)

AF:

0.00000713

AC:

AN:

981160

Other (OTH)

AF:

0.0000211

AC:

AN:

47396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000104

AC:

AN:

125490

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

AN XY:

59112

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33294

American (AMR)

AF:

0.000675

AC:

AN:

10364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3220

East Asian (EAS)

AF:

0.00

AC:

AN:

3686

South Asian (SAS)

AF:

0.00

AC:

AN:

3656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

222

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62102

Other (OTH)

AF:

0.00

AC:

AN:

1764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.00000840

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.097

MetaSVM

Uncertain

-0.19

PhyloP100

-0.20

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.18

REVEL

Benign

0.16

Sift

Uncertain

0.017

Vest4

0.19

MutPred

0.35

Loss of MoRF binding (P = 0.0077)

MVP

0.57

MPC

0.64

ClinPred

0.15

GERP RS

0.60

PromoterAI

-0.0049

Neutral

(source)

Varity_R

0.10

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over