chr20-34990473-C-T

Position:

• chr20-34990473-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020884.7(MYH7B):​c.1977+163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 929,684 control chromosomes in the GnomAD database, including 745 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 0.044 (487 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (258 hom.)
• Consequence: MYH7B NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424

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]

MIR499A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7B	NM_020884.7	c.1977+163C>T		intron_variant		ENST00000262873.13	NP_065935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13	c.1977+163C>T		intron_variant		1	NM_020884.7	ENSP00000262873.8
MIR499A	ENST00000384903.1	n.98C>T		non_coding_transcript_exon_variant	1/1	6
MIR499B	ENST00000636498.1	n.-1G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6743 AN: 152148 Hom.: 486 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0382

GnomAD3 exomes AF: 0.0126 AC: 3150 AN: 249554 Hom.: 201 AF XY: 0.00981 AC XY: 1326 AN XY: 135176

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.00718

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00104

Gnomad SAS exome AF: 0.00988

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000498

Gnomad OTH exome AF: 0.00589

GnomAD4 exome AF: 0.00637 AC: 4950 AN: 777418 Hom.: 258 Cov.: 11 AF XY: 0.00561 AC XY: 2316 AN XY: 412512

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.00826

Gnomad4 ASJ exome AF: 0.0000457

Gnomad4 EAS exome AF: 0.00104

Gnomad4 SAS exome AF: 0.00997

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000476

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0443 AC: 6751 AN: 152266 Hom.: 487 Cov.: 32 AF XY: 0.0417 AC XY: 3108 AN XY: 74458

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0220 Hom.: 106

Bravo AF: 0.0492

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.86

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: rs7267163; hg19: chr20-33578276;