3-151371438-C-T

Variant names:

• chr3-151371438-C-T
• rs7637803
• NM_001393769.1:c.3665-1129C>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.3665-1129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,108 control chromosomes in the GnomAD database, including 4,517 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 0.23 (4517 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• 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, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.3665-1129C>T		intron_variant	Intron 26 of 44	ENST00000687756.1	NP_001380698.1
P2RY12	NM_022788.5	c.-180+13254G>A		intron_variant	Intron 1 of 2	ENST00000302632.4	NP_073625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.3665-1129C>T		intron_variant	Intron 26 of 44		NM_001393769.1	ENSP00000508695.1
P2RY12	ENST00000302632.4	c.-180+13254G>A		intron_variant	Intron 1 of 2	1	NM_022788.5	ENSP00000307259.4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35517 AN: 151990 Hom.: 4500 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.234 AC: 35574 AN: 152108 Hom.: 4517 Cov.: 32 AF XY: 0.228 AC XY: 16970 AN XY: 74350

African (AFR) AF: 0.333 AC: 13797 AN: 41466

American (AMR) AF: 0.175 AC: 2674 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3470

East Asian (EAS) AF: 0.170 AC: 884 AN: 5188

South Asian (SAS) AF: 0.168 AC: 813 AN: 4826

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10588

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13840 AN: 67978

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.220 Hom.: 12135

Bravo AF: 0.240

Asia WGS AF: 0.171 AC: 595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		-0.57
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: rs7637803; hg19: chr3-151089226;