chr20-34990448-A-G

Variant names:

• chr20-34990448-A-G
• rs3746444
• NM_020884.7:c.1977+138A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020884.7(MYH7B):​c.1977+138A>G variant causes a intron change. The variant allele was found at a frequency of 0.194 in 992,462 control chromosomes in the GnomAD database, including 19,861 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 0.19 (2720 hom., cov: 32)
  • Exomes 𝑓: 0.20 (17141 hom.)
• Consequence: MYH7B NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64
• Publications: 532 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]

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 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.1977+138A>G		intron	N/A	NP_065935.4
	MIR499A	NR_030223.1		n.73A>G		non_coding_transcript_exon	Exon 1 of 1
	MIR499B	NR_039912.1		n.25T>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.1977+138A>G		intron	N/A	ENSP00000262873.8
	MIR499A	ENST00000384903.1	TSL:6	n.73A>G		non_coding_transcript_exon	Exon 1 of 1
	MIR499B	ENST00000636498.1	TSL:6	n.25T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28298 AN: 152012 Hom.: 2718 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.196 AC: 49000 AN: 250094 AF XY: 0.204

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.147

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.195 AC: 164066 AN: 840334 Hom.: 17141 Cov.: 12 AF XY: 0.200 AC XY: 88597 AN XY: 442508

African (AFR) AF: 0.181 AC: 3899 AN: 21558

American (AMR) AF: 0.117 AC: 5142 AN: 43960

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 6825 AN: 22262

East Asian (EAS) AF: 0.161 AC: 5943 AN: 36880

South Asian (SAS) AF: 0.259 AC: 18908 AN: 73050

European-Finnish (FIN) AF: 0.199 AC: 10546 AN: 52930

Middle Eastern (MID) AF: 0.335 AC: 1531 AN: 4564

European-Non Finnish (NFE) AF: 0.190 AC: 103335 AN: 545122

Other (OTH) AF: 0.198 AC: 7937 AN: 40008

GnomAD4 genome AF: 0.186 AC: 28311 AN: 152128 Hom.: 2720 Cov.: 32 AF XY: 0.187 AC XY: 13890 AN XY: 74382

African (AFR) AF: 0.173 AC: 7167 AN: 41510

American (AMR) AF: 0.154 AC: 2355 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3472

East Asian (EAS) AF: 0.144 AC: 739 AN: 5146

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4814

European-Finnish (FIN) AF: 0.199 AC: 2108 AN: 10586

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12898 AN: 67978

Other (OTH) AF: 0.201 AC: 425 AN: 2114

Alfa AF: 0.193 Hom.: 10948

Bravo AF: 0.182

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.87
PhyloP100		5.6
Mutation Taster		=99/1	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: rs3746444; hg19: chr20-33578251; COSMIC: COSV53420431;