rs1491974

Variant names:

• chr3-151384664-A-G
• rs1491974
• NM_001393769.1:c.4927-366A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

P2RY12 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 8

  Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393769.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	NM_001393769.1	MANE Select	c.4927-366A>G		intron	N/A	NP_001380698.1	A0A8I5KX78
	P2RY12	NM_022788.5	MANE Select	c.-180+28T>C		intron	N/A	NP_073625.1	Q9H244
	MED12L	NM_053002.6		c.4822-366A>G		intron	N/A	NP_443728.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	ENST00000687756.1	MANE Select	c.4927-366A>G		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	P2RY12	ENST00000302632.4	TSL:1 MANE Select	c.-180+28T>C		intron	N/A	ENSP00000307259.4	Q9H244
	MED12L	ENST00000474524.5	TSL:1	c.4822-366A>G		intron	N/A	ENSP00000417235.1	Q86YW9-1

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

African (AFR) AF: 0.503 AC: 602 AN: 1198

American (AMR) AF: 0.545 AC: 699 AN: 1282

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 818 AN: 1490

East Asian (EAS) AF: 0.489 AC: 940 AN: 1924

South Asian (SAS) AF: 0.449 AC: 1404 AN: 3130

European-Finnish (FIN) AF: 0.526 AC: 1255 AN: 2384

Middle Eastern (MID) AF: 0.608 AC: 129 AN: 212

European-Non Finnish (NFE) AF: 0.482 AC: 15012 AN: 31128

Other (OTH) AF: 0.496 AC: 1502 AN: 3026

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

African (AFR) AF: 0.499 AC: 20672 AN: 41418

American (AMR) AF: 0.526 AC: 8028 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3470

East Asian (EAS) AF: 0.536 AC: 2764 AN: 5158

South Asian (SAS) AF: 0.484 AC: 2330 AN: 4814

European-Finnish (FIN) AF: 0.538 AC: 5658 AN: 10512

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33149 AN: 67962

Other (OTH) AF: 0.544 AC: 1149 AN: 2114

Alfa AF: 0.493 Hom.: 8023

Bravo AF: 0.504

Asia WGS AF: 0.504 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.96
DANN	Benign	0.62
PhyloP100		-0.76
PromoterAI		-0.032	Neutral
Mutation Taster		=100/0	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: rs1491974; hg19: chr3-151102452;