chr20-34977663-C-T

Position:

• chr20-34977663-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.343

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 136 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7B	NM_020884.7	c.-90C>T		5_prime_UTR_variant	4/45	ENST00000262873.13	NP_065935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13	c.-90C>T		5_prime_UTR_variant	4/45	1	NM_020884.7	ENSP00000262873	P1
MYH7B	ENST00000673749.1	n.445C>T		non_coding_transcript_exon_variant	4/9
MYH7B	ENST00000470929.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000904 AC: 136 AN: 150404 Hom.: 0 Cov.: 29

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

GnomAD3 exomes AF: 0.00123 AC: 250 AN: 202672 Hom.: 0 AF XY: 0.00136 AC XY: 147 AN XY: 108452

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 SAS exome AF: 0.00399

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.: 8 Cov.: 31 AF XY: 0.000683 AC XY: 482 AN XY: 705988

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00363

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000259

Gnomad4 OTH exome AF: 0.000967

GnomAD4 genome AF: 0.000903 AC: 136 AN: 150536 Hom.: 0 Cov.: 29 AF XY: 0.000912 AC XY: 67 AN XY: 73502

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.00112

Gnomad4 ASJ AF: 0.00116

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00298

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000384

Gnomad4 OTH AF: 0.000960

Alfa AF: 0.000735 Hom.: 1

Bravo AF: 0.00107

ESP6500AA AF: 0.00225 AC: 9

ESP6500EA AF: 0.000480 AC: 4

ExAC AF: 0.00115 AC: 137

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 27, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	MYH7B: BP4 -

MYH7B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.014
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.53	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0067	T;T
MetaSVM	Benign	-0.42	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.080	N;.
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;.
Vest4		0.20
MVP		0.56
MPC		0.52
ClinPred		0.047	T
GERP RS		1.4
Varity_R		0.081
gMVP		0.55

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

Other links and lift over

dbSNP: rs201494323; hg19: chr20-33565466;