chr20-34959830-T-G

Variant names:

• chr20-34959830-T-G
• rs6088662
• NM_020884.7:c.-222+1618T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020884.7(MYH7B):​c.-222+1618T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,170 control chromosomes in the GnomAD database, including 2,979 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (2979 hom., cov: 32)
• Consequence: MYH7B NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 25 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	NM_020884.7	MANE Select	c.-222+1618T>G		intron	N/A	NP_065935.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.-222+1618T>G		intron	N/A	ENSP00000262873.8
	MYH7B	ENST00000673749.1		n.313+1618T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29756 AN: 152052 Hom.: 2977 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29776 AN: 152170 Hom.: 2979 Cov.: 32 AF XY: 0.196 AC XY: 14579 AN XY: 74412

African (AFR) AF: 0.192 AC: 7968 AN: 41514

American (AMR) AF: 0.162 AC: 2476 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3472

East Asian (EAS) AF: 0.140 AC: 726 AN: 5170

South Asian (SAS) AF: 0.267 AC: 1287 AN: 4814

European-Finnish (FIN) AF: 0.205 AC: 2178 AN: 10606

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13355 AN: 67984

Other (OTH) AF: 0.209 AC: 442 AN: 2112

Alfa AF: 0.197 Hom.: 2057

Bravo AF: 0.192

Asia WGS AF: 0.226 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.56
PhyloP100		-0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6088662; hg19: chr20-33547633;