rs1920395

Positions:

• chr3-151252898-G-A
• chr3-151252898-G-C

Variant summary

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

The NM_001393769.1(MED12L):​c.2250+59232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,830 control chromosomes in the GnomAD database, including 10,489 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 0.37 (10489 hom., cov: 31)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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]

P2RY14 (HGNC:16442): (purinergic receptor P2Y14) The product of this gene belongs to the family of G-protein coupled receptors, which contains several receptor subtypes with different pharmacological selectivity for various adenosine and uridine nucleotides. This receptor is a P2Y purinergic receptor for UDP-glucose and other UDP-sugars coupled to G-proteins. It has been implicated in extending the known immune system functions of P2Y receptors by participating in the regulation of the stem cell compartment, and it may also play a role in neuroimmune function. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.2250+59232G>A		intron_variant		ENST00000687756.1	NP_001380698.1
P2RY14	NM_014879.4	c.-133+25389C>T		intron_variant		ENST00000309170.8	NP_055694.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY14	ENST00000309170.8	c.-133+25389C>T		intron_variant		1	NM_014879.4	ENSP00000308361	P1
MED12L	ENST00000687756.1	c.2250+59232G>A		intron_variant			NM_001393769.1	ENSP00000508695	A2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55629 AN: 151712 Hom.: 10479 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.367 AC: 55662 AN: 151830 Hom.: 10489 Cov.: 31 AF XY: 0.375 AC XY: 27803 AN XY: 74192

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.392

Alfa AF: 0.343 Hom.: 8774

Bravo AF: 0.369

Asia WGS AF: 0.512 AC: 1783 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.58
DANN	Benign	0.25

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: rs1920395; hg19: chr3-150970686;