rs11922647

Variant names:

• chr3-151341491-G-A
• rs11922647
• NM_001393769.1:c.2251-8568G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393769.1(MED12L):​c.2251-8568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 151,926 control chromosomes in the GnomAD database, including 54,544 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 0.85 (54544 hom., cov: 30)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.877 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.2251-8568G>A		intron	N/A	NP_001380698.1	A0A8I5KX78
	P2RY12	NM_022788.5	MANE Select	c.-179-731C>T		intron	N/A	NP_073625.1	Q9H244
	MED12L	NM_053002.6		c.2146-8568G>A		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.2251-8568G>A		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	P2RY12	ENST00000302632.4	TSL:1 MANE Select	c.-179-731C>T		intron	N/A	ENSP00000307259.4	Q9H244
	MED12L	ENST00000474524.5	TSL:1	c.2146-8568G>A		intron	N/A	ENSP00000417235.1	Q86YW9-1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128610 AN: 151808 Hom.: 54513 Cov.: 30

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.882

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.847 AC: 128698 AN: 151926 Hom.: 54544 Cov.: 30 AF XY: 0.849 AC XY: 63075 AN XY: 74260

African (AFR) AF: 0.856 AC: 35448 AN: 41410

American (AMR) AF: 0.867 AC: 13218 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3049 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4394 AN: 5174

South Asian (SAS) AF: 0.900 AC: 4337 AN: 4820

European-Finnish (FIN) AF: 0.842 AC: 8870 AN: 10536

Middle Eastern (MID) AF: 0.952 AC: 278 AN: 292

European-Non Finnish (NFE) AF: 0.832 AC: 56566 AN: 67958

Other (OTH) AF: 0.878 AC: 1850 AN: 2108

Alfa AF: 0.845 Hom.: 7035

Bravo AF: 0.849

Asia WGS AF: 0.840 AC: 2915 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.30
PhyloP100		-2.4
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: rs11922647; hg19: chr3-151059279;