rs7811

Positions:

• chr18-3256114-A-G
• chr18-3256114-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006471.4(MYL12A):​c.*196A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 685,152 control chromosomes in the GnomAD database, including 8,188 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 0.15 (1812 hom., cov: 33)
  • Exomes 𝑓: 0.15 (6376 hom.)
• Consequence: MYL12A NM_006471.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877

Genes affected

MYL12A (HGNC:16701): (myosin light chain 12A) This gene encodes a nonsarcomeric myosin regulatory light chain. This protein is activated by phosphorylation and regulates smooth muscle and non-muscle cell contraction. This protein may also be involved in DNA damage repair by sequestering the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 which functions as a repressor of p53-driven apoptosis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8.[provided by RefSeq, Dec 2014]

MYL12-AS1 (HGNC:55331): (MYL12A and MYL12B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL12A	NM_006471.4	c.*196A>G		3_prime_UTR_variant	4/4	ENST00000217652.8	NP_006462.1
MYL12-AS1	NR_130145.1	n.447+128T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL12A	ENST00000217652.8	c.*196A>G		3_prime_UTR_variant	4/4	1	NM_006471.4	ENSP00000217652	P1
MYL12-AS1	ENST00000581905.2	n.322+128T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22775 AN: 152092 Hom.: 1805 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.146 AC: 77642 AN: 532942 Hom.: 6376 Cov.: 7 AF XY: 0.146 AC XY: 40508 AN XY: 277802

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0772

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.150 AC: 22819 AN: 152210 Hom.: 1812 Cov.: 33 AF XY: 0.155 AC XY: 11540 AN XY: 74412

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.135

Alfa AF: 0.125 Hom.: 2449

Bravo AF: 0.138

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7811; hg19: chr18-3256112;