rs868150

Positions:

• chr17-40057106-A-G
• chr17-40057106-A-T

Variant summary

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

The ENST00000585306.5(MED24):​c.-37-3471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,776 control chromosomes in the GnomAD database, including 29,159 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 0.62 (29159 hom., cov: 30)
• Consequence: MED24 ENST00000585306.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

MED24 (HGNC:22963): (mediator complex subunit 24) This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000585306.5	c.-37-3471T>C		intron_variant		4		ENSP00000462646

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93718 AN: 151658 Hom.: 29139 Cov.: 30

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.618 AC: 93782 AN: 151776 Hom.: 29159 Cov.: 30 AF XY: 0.620 AC XY: 45967 AN XY: 74156

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.637

Alfa AF: 0.588 Hom.: 11397

Bravo AF: 0.629

Asia WGS AF: 0.627 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs868150; hg19: chr17-38213359;