20-34977677-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020884.7(MYH7B):c.-76C>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 0.303 in 1,471,412 control chromosomes in the GnomAD database, including 65,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (5976 hom., cov: 23)
  • Exomes 𝑓: 0.30 (59253 hom.)
• Consequence: MYH7B NM_020884.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0670

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 20-34977677-C-T is Benign according to our data. Variant chr20-34977677-C-T is described in ClinVar as [Benign]. Clinvar id is 1543896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7B	NM_020884.7	c.-76C>T		5_prime_UTR_variant	4/45	ENST00000262873.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7B	ENST00000262873.13	c.-76C>T		5_prime_UTR_variant	4/45	1	NM_020884.7	P1
MYH7B	ENST00000470929.5	n.11C>T		non_coding_transcript_exon_variant	1/6	2
MYH7B	ENST00000673749.1	n.459C>T		non_coding_transcript_exon_variant	4/9

Frequencies

GnomAD3 genomes AF: 0.330 AC: 41147 AN: 124708 Hom.: 5976 Cov.: 23

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.238 AC: 45683 AN: 191614 Hom.: 5843 AF XY: 0.241 AC XY: 24682 AN XY: 102392

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.234

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.301 AC: 405124 AN: 1346640 Hom.: 59253 Cov.: 36 AF XY: 0.300 AC XY: 199435 AN XY: 665150

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.330 AC: 41161 AN: 124772 Hom.: 5976 Cov.: 23 AF XY: 0.331 AC XY: 19640 AN XY: 59300

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.307

Alfa AF: 0.271 Hom.: 11593

Bravo AF: 0.271

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	7.7
Dann	Benign	0.69

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: rs6060137; hg19: chr20-33565480; COSMIC: COSV53418959; COSMIC: COSV53418959;