chr20-34990473-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.424

Publications

12 publications found

Variant links:

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 links:

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]

MIR499A links:

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]

MIR499B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYH7B	NM_020884.7 link	c.1977+163C>T		intron_variant	Intron 22 of 44	ENST00000262873.13	NP_065935.4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MYH7B	ENST00000262873.13 link	c.1977+163C>T	intron_variant	Intron 22 of 44	1	NM_020884.7	ENSP00000262873.8
MIR499A	ENST00000384903.1 link	n.98C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR499B	ENST00000636498.1 link	n.-1G>A	upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6743

AN:

152148

Hom.:

486

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0126

AC:

3150

AN:

249554

AF XY:

0.00981

show subpopulations

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 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.:

AF XY:

0.00561

AC XY:

2316

AN XY:

412512

show subpopulations

African (AFR)

AF:

0.153

AC:

3114

AN:

20332

American (AMR)

AF:

0.00826

AC:

362

AN:

43826

Ashkenazi Jewish (ASJ)

AF:

0.0000457

AC:

AN:

21898

East Asian (EAS)

AF:

0.00104

AC:

AN:

36492

South Asian (SAS)

AF:

0.00997

AC:

717

AN:

71902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52822

Middle Eastern (MID)

AF:

0.00720

AC:

AN:

4442

European-Non Finnish (NFE)

AF:

0.000476

AC:

232

AN:

487782

Other (OTH)

AF:

0.0120

AC:

454

AN:

37922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

250

500

750

1000

1250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0443

AC:

6751

AN:

152266

Hom.:

487

Cov.:

AF XY:

0.0417

AC XY:

3108

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.153

AC:

6364

AN:

41530

American (AMR)

AF:

0.0142

AC:

218

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000969

AC:

AN:

5162

South Asian (SAS)

AF:

0.0104

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68028

Other (OTH)

AF:

0.0378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

287

573

860

1146

1433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0257

Hom.:

136

Bravo

AF:

0.0492

Asia WGS

AF:

0.0190

AC:

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

(source)

DANN

Benign

0.86

PhyloP100

0.42

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over