3-151324676-A-G

Position:

• chr3-151324676-A-G

Variant summary

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

The NM_001393769.1(MED12L):​c.2251-25383A>G 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 152,044 control chromosomes in the GnomAD database, including 7,282 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 (7282 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED12L	NM_001393769.1	c.2251-25383A>G		intron_variant		ENST00000687756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED12L	ENST00000687756.1	c.2251-25383A>G		intron_variant			NM_001393769.1	A2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46902 AN: 151926 Hom.: 7284 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.309 AC: 46935 AN: 152044 Hom.: 7282 Cov.: 32 AF XY: 0.309 AC XY: 22977 AN XY: 74302

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.302

Alfa AF: 0.310 Hom.: 3320

Bravo AF: 0.303

Asia WGS AF: 0.255 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
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

Other links and lift over

dbSNP: rs12107539; hg19: chr3-151042464;