rs7267163

Positions:

• 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:32133): (microRNA 499a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR499B (HGNC:41640): (microRNA 499b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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	UniProt
MYH7B	NM_020884.7	c.1977+163C>T		intron_variant		ENST00000262873.13
MIR499A	NR_030223.1	n.98C>T		non_coding_transcript_exon_variant	1/1
MIR499B	NR_039912.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7B	ENST00000262873.13	c.1977+163C>T		intron_variant		1	NM_020884.7	P1
MIR499A	ENST00000384903.1	n.98C>T		non_coding_transcript_exon_variant	1/1
MIR499B	ENST00000636498.1			upstream_gene_variant

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;