rs1491974

Positions:

• chr3-151384664-A-G
• chr3-151384664-A-T

Variant summary

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

The NM_001393769.1(MED12L):​c.4927-366A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 197,694 control chromosomes in the GnomAD database, including 24,878 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 0.50 (19294 hom., cov: 32)
  • Exomes 𝑓: 0.49 (5584 hom.)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755

Genes affected

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

P2RY12 (HGNC:18124): (purinergic receptor P2Y12) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.4927-366A>G		intron_variant		ENST00000687756.1	NP_001380698.1
P2RY12	NM_022788.5	c.-180+28T>C		intron_variant		ENST00000302632.4	NP_073625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.4927-366A>G		intron_variant			NM_001393769.1	ENSP00000508695.1
P2RY12	ENST00000302632.4	c.-180+28T>C		intron_variant		1	NM_022788.5	ENSP00000307259.4

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76333 AN: 151802 Hom.: 19274 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.489 AC: 22361 AN: 45774 Hom.: 5584 Cov.: 0 AF XY: 0.487 AC XY: 11291 AN XY: 23208

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.503 AC: 76395 AN: 151920 Hom.: 19294 Cov.: 32 AF XY: 0.507 AC XY: 37590 AN XY: 74214

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.544

Alfa AF: 0.489 Hom.: 5108

Bravo AF: 0.504

Asia WGS AF: 0.504 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.96
DANN	Benign	0.62

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: rs1491974; hg19: chr3-151102452;