3-151342280-C-T

Position:

• chr3-151342280-C-T

Variant summary

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

The NM_001393769.1(MED12L):​c.2251-7779C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,136 control chromosomes in the GnomAD database, including 7,553 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 0.31 (7553 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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]

MED12L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.2251-7779C>T		intron_variant		ENST00000687756.1	NP_001380698.1
P2RY12	NM_022788.5	c.-179-1520G>A		intron_variant		ENST00000302632.4	NP_073625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.2251-7779C>T		intron_variant			NM_001393769.1	ENSP00000508695.1
P2RY12	ENST00000302632.4	c.-179-1520G>A		intron_variant		1	NM_022788.5	ENSP00000307259.4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46998 AN: 152020 Hom.: 7546 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.309 AC: 47035 AN: 152136 Hom.: 7553 Cov.: 32 AF XY: 0.315 AC XY: 23405 AN XY: 74372

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.353

Alfa AF: 0.250 Hom.: 1253

Bravo AF: 0.315

Asia WGS AF: 0.423 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16863323; hg19: chr3-151060068;