17-12760379-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001146312.3(MYOCD):​c.2332-271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 420,866 control chromosomes in the GnomAD database, including 31,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 9047 hom., cov: 33)
Exomes 𝑓: 0.39 ( 22101 hom. )

Consequence

MYOCD
NM_001146312.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.402
Variant links:
Genes affected
MYOCD (HGNC:16067): (myocardin) This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
ARHGAP44-AS1 (HGNC:55326): (ARHGAP44 and MYOCD antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 17-12760379-G-A is Benign according to our data. Variant chr17-12760379-G-A is described in ClinVar as [Benign]. Clinvar id is 1272626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYOCDNM_001146312.3 linkuse as main transcriptc.2332-271G>A intron_variant ENST00000425538.6
ARHGAP44-AS1NR_104607.1 linkuse as main transcriptn.3482C>T non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYOCDENST00000425538.6 linkuse as main transcriptc.2332-271G>A intron_variant 1 NM_001146312.3 P2Q8IZQ8-3
MYOCDENST00000343344.8 linkuse as main transcriptc.2188-271G>A intron_variant 1 A2Q8IZQ8-1
MYOCDENST00000443061.1 linkuse as main transcriptc.1318-271G>A intron_variant 1
ARHGAP44-AS1ENST00000584772.1 linkuse as main transcriptn.3440C>T non_coding_transcript_exon_variant 2/21

Frequencies

GnomAD3 genomes
AF:
0.312
AC:
47512
AN:
152048
Hom.:
9046
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0895
Gnomad AMI
AF:
0.429
Gnomad AMR
AF:
0.358
Gnomad ASJ
AF:
0.329
Gnomad EAS
AF:
0.570
Gnomad SAS
AF:
0.416
Gnomad FIN
AF:
0.426
Gnomad MID
AF:
0.322
Gnomad NFE
AF:
0.390
Gnomad OTH
AF:
0.337
GnomAD4 exome
AF:
0.394
AC:
105738
AN:
268700
Hom.:
22101
Cov.:
0
AF XY:
0.396
AC XY:
56077
AN XY:
141468
show subpopulations
Gnomad4 AFR exome
AF:
0.0910
Gnomad4 AMR exome
AF:
0.389
Gnomad4 ASJ exome
AF:
0.330
Gnomad4 EAS exome
AF:
0.592
Gnomad4 SAS exome
AF:
0.414
Gnomad4 FIN exome
AF:
0.410
Gnomad4 NFE exome
AF:
0.388
Gnomad4 OTH exome
AF:
0.378
GnomAD4 genome
AF:
0.312
AC:
47510
AN:
152166
Hom.:
9047
Cov.:
33
AF XY:
0.318
AC XY:
23674
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0893
Gnomad4 AMR
AF:
0.358
Gnomad4 ASJ
AF:
0.329
Gnomad4 EAS
AF:
0.570
Gnomad4 SAS
AF:
0.415
Gnomad4 FIN
AF:
0.426
Gnomad4 NFE
AF:
0.390
Gnomad4 OTH
AF:
0.336
Alfa
AF:
0.347
Hom.:
1237
Bravo
AF:
0.296
Asia WGS
AF:
0.466
AC:
1622
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.0
DANN
Benign
0.54

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56138813; hg19: chr17-12663696; API