chr20-34977677-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020884.7(MYH7B):​c.-76C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000668 in 1,347,896 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: MYH7B NM_020884.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 20-34977677-C-G is Benign according to our data. Variant chr20-34977677-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1662428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 9 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.-76C>G		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>G		5_prime_UTR	Exon 4 of 45	ENSP00000262873.8	A7E2Y1-4
	MYH7B	ENST00000971120.1		c.-14C>G		5_prime_UTR	Exon 1 of 41	ENSP00000641179.1
	MYH7B	ENST00000470929.5	TSL:2	n.11C>G		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000157 AC: 3 AN: 191614 AF XY: 0.00000977

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000668 AC: 9 AN: 1347896 Hom.: 0 Cov.: 36 AF XY: 0.0000105 AC XY: 7 AN XY: 665768

African (AFR) AF: 0.00 AC: 0 AN: 31054

American (AMR) AF: 0.00 AC: 0 AN: 35270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22204

East Asian (EAS) AF: 0.00 AC: 0 AN: 29038

South Asian (SAS) AF: 0.0000994 AC: 8 AN: 80466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5164

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046434

Other (OTH) AF: 0.0000185 AC: 1 AN: 53960

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.3
DANN	Benign	0.57
PhyloP100		-0.067
PromoterAI		-0.0066	Neutral
Mutation Taster		=100/0	polymorphism

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;