20-34977677-C-T

Variant names:

• chr20-34977677-C-T
• rs6060137
• NM_020884.7:c.-76C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020884.7(MYH7B):​c.-76C>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 0.303 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_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0670
• Publications: 16 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1543896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 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.-76C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 45	NP_065935.4	A7E2Y1-4
	MYH7B	NM_020884.7	MANE Select	c.-76C>T		5_prime_UTR	Exon 4 of 45	NP_065935.4	A7E2Y1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.-76C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 45	ENSP00000262873.8	A7E2Y1-4
	MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.-76C>T		5_prime_UTR	Exon 4 of 45	ENSP00000262873.8	A7E2Y1-4
	MYH7B	ENST00000971120.1		c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 41	ENSP00000641179.1

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

GnomAD2 exomes AF: 0.238 AC: 45683 AN: 191614 AF XY: 0.241

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 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

African (AFR) AF: 0.353 AC: 10967 AN: 31030

American (AMR) AF: 0.140 AC: 4922 AN: 35252

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 5177 AN: 22188

East Asian (EAS) AF: 0.277 AC: 8029 AN: 28994

South Asian (SAS) AF: 0.289 AC: 23234 AN: 80398

European-Finnish (FIN) AF: 0.243 AC: 10780 AN: 44276

Middle Eastern (MID) AF: 0.157 AC: 812 AN: 5162

European-Non Finnish (NFE) AF: 0.311 AC: 324860 AN: 1045408

Other (OTH) AF: 0.303 AC: 16343 AN: 53932

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

African (AFR) AF: 0.396 AC: 13374 AN: 33798

American (AMR) AF: 0.287 AC: 2913 AN: 10160

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 701 AN: 3086

East Asian (EAS) AF: 0.293 AC: 1128 AN: 3846

South Asian (SAS) AF: 0.348 AC: 1363 AN: 3916

European-Finnish (FIN) AF: 0.305 AC: 2088 AN: 6854

Middle Eastern (MID) AF: 0.301 AC: 53 AN: 176

European-Non Finnish (NFE) AF: 0.313 AC: 18895 AN: 60464

Other (OTH) AF: 0.307 AC: 530 AN: 1728

Alfa AF: 0.274 Hom.: 25256

Bravo AF: 0.271

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.7
DANN	Benign	0.69
PhyloP100		-0.067
PromoterAI		-0.032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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