rs11615689

chr12-116261870-T-C

Variant summary

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

The NM_015335.5(MED13L):c.72+15190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,240 control chromosomes in the GnomAD database, including 1,938 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 0.15 (1938 hom., cov: 32)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

Genes affected

MED13L (HGNC:22962): (mediator complex subunit 13L) The protein encoded by this gene is a subunit of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase II-transcribed genes. The encoded protein is involved in early development of the heart and brain. Defects in this gene are a cause of transposition of the great arteries, dextro-looped (DTGA).[provided by RefSeq, Jul 2010]

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 (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED13L	NM_015335.5	c.72+15190A>G		intron_variant		ENST00000281928.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED13L	ENST00000281928.9	c.72+15190A>G		intron_variant		1	NM_015335.5	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22640 AN: 152122 Hom.: 1935 Cov.: 32

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.149 AC: 22653 AN: 152240 Hom.: 1938 Cov.: 32 AF XY: 0.152 AC XY: 11337 AN XY: 74442

Gnomad4 AFR AF: 0.0680

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.184

Alfa AF: 0.177 Hom.: 1221

Bravo AF: 0.136

Asia WGS AF: 0.204 AC: 709 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	2.9
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: rs11615689; hg19: chr12-116699675;