chr17-40025976-G-T

Position:

• chr17-40025976-G-T

Variant summary

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

The ENST00000394128.7(MED24):​c.1985+180C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,048 control chromosomes in the GnomAD database, including 9,463 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 0.34 (9463 hom., cov: 32)
• Consequence: MED24 ENST00000394128.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED24	NM_014815.4	c.1985+180C>A		intron_variant		ENST00000394128.7	NP_055630.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7	c.1985+180C>A		intron_variant		1	NM_014815.4	ENSP00000377686	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52326 AN: 151930 Hom.: 9471 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.344 AC: 52325 AN: 152048 Hom.: 9463 Cov.: 32 AF XY: 0.346 AC XY: 25683 AN XY: 74322

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.384

Alfa AF: 0.372 Hom.: 5297

Bravo AF: 0.349

Asia WGS AF: 0.420 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9916158; hg19: chr17-38182229;