20-34991096-T-C

Variant names:

• chr20-34991096-T-C
• rs2425009
• NM_020884.7:c.2158T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020884.7(MYH7B):​c.2158T>C​(p.Leu720Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,611,862 control chromosomes in the GnomAD database, including 429,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45513 hom., cov: 33)
  • Exomes 𝑓: 0.72 (383878 hom.)
• Consequence: MYH7B NM_020884.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.09
• Publications: 20 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 20-34991096-T-C is Benign according to our data. Variant chr20-34991096-T-C is described in ClinVar as Benign. ClinVar VariationId is 1601513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 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.2158T>C	p.Leu720Leu	synonymous	Exon 24 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.2158T>C	p.Leu720Leu	synonymous	Exon 24 of 45	ENSP00000262873.8	A7E2Y1-4
	MYH7B	ENST00000888939.1		c.2122T>C	p.Leu708Leu	synonymous	Exon 19 of 40	ENSP00000558998.1
	MYH7B	ENST00000971120.1		c.2122T>C	p.Leu708Leu	synonymous	Exon 20 of 41	ENSP00000641179.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117147 AN: 152060 Hom.: 45465 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.783

GnomAD2 exomes AF: 0.768 AC: 189964 AN: 247492 AF XY: 0.761

Gnomad AFR exome AF: 0.825

Gnomad AMR exome AF: 0.891

Gnomad ASJ exome AF: 0.792

Gnomad EAS exome AF: 0.761

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.730

Gnomad OTH exome AF: 0.783

GnomAD4 exome AF: 0.723 AC: 1055837 AN: 1459684 Hom.: 383878 Cov.: 43 AF XY: 0.724 AC XY: 525448 AN XY: 726072

African (AFR) AF: 0.825 AC: 27615 AN: 33454

American (AMR) AF: 0.885 AC: 39446 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 20627 AN: 25972

East Asian (EAS) AF: 0.789 AC: 31332 AN: 39686

South Asian (SAS) AF: 0.713 AC: 61290 AN: 86002

European-Finnish (FIN) AF: 0.792 AC: 42237 AN: 53304

Middle Eastern (MID) AF: 0.869 AC: 4997 AN: 5750

European-Non Finnish (NFE) AF: 0.706 AC: 783995 AN: 1110642

Other (OTH) AF: 0.735 AC: 44298 AN: 60300

GnomAD4 genome AF: 0.771 AC: 117255 AN: 152178 Hom.: 45513 Cov.: 33 AF XY: 0.774 AC XY: 57591 AN XY: 74400

African (AFR) AF: 0.823 AC: 34156 AN: 41520

American (AMR) AF: 0.822 AC: 12562 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2769 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4004 AN: 5166

South Asian (SAS) AF: 0.706 AC: 3405 AN: 4826

European-Finnish (FIN) AF: 0.802 AC: 8508 AN: 10608

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49153 AN: 67978

Other (OTH) AF: 0.785 AC: 1659 AN: 2114

Alfa AF: 0.752 Hom.: 21004

Bravo AF: 0.780

Asia WGS AF: 0.766 AC: 2664 AN: 3478

EpiCase AF: 0.739

EpiControl AF: 0.745

ClinVar

ClinVar submissions as Germline

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	-0.63
CADD	Benign	9.8
DANN	Benign	0.79
PhyloP100		2.1
Mutation Taster		=98/2	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: rs2425009; hg19: chr20-33578899; COSMIC: COSV108074564; COSMIC: COSV108074564;