rs11922647

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.35
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MED12LNM_001393769.1 linkuse as main transcriptc.2251-8568G>A intron_variant ENST00000687756.1
P2RY12NM_022788.5 linkuse as main transcriptc.-179-731C>T intron_variant ENST00000302632.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
P2RY12ENST00000302632.4 linkuse as main transcriptc.-179-731C>T intron_variant 1 NM_022788.5 P1
MED12LENST00000687756.1 linkuse as main transcriptc.2251-8568G>A intron_variant NM_001393769.1 A2

Frequencies

GnomAD3 genomes
AF:
0.847
AC:
128610
AN:
151808
Hom.:
54513
Cov.:
30
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.856
Gnomad4 AMR
AF:
0.867
Gnomad4 ASJ
AF:
0.879
Gnomad4 EAS
AF:
0.849
Gnomad4 SAS
AF:
0.900
Gnomad4 FIN
AF:
0.842
Gnomad4 NFE
AF:
0.832
Gnomad4 OTH
AF:
0.878
Alfa
AF:
0.843
Hom.:
6726
Bravo
AF:
0.849
Asia WGS
AF:
0.840
AC:
2915
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.10
DANN
Benign
0.30

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11922647; hg19: chr3-151059279; API