17-40019300-C-T

Position:

• chr17-40019300-C-T

Variant summary

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

The NM_014815.4(MED24):​c.*229G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 550,078 control chromosomes in the GnomAD database, including 38,048 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 0.36 (9960 hom., cov: 32)
  • Exomes 𝑓: 0.37 (28088 hom.)
• Consequence: MED24 NM_014815.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED24	NM_014815.4	c.*229G>A		3_prime_UTR_variant	26/26	ENST00000394128.7	NP_055630.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7	c.*229G>A		3_prime_UTR_variant	26/26	1	NM_014815.4	ENSP00000377686	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54783 AN: 151614 Hom.: 9942 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.368 AC: 146710 AN: 398346 Hom.: 28088 Cov.: 3 AF XY: 0.361 AC XY: 75527 AN XY: 209184

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.362 AC: 54861 AN: 151732 Hom.: 9960 Cov.: 32 AF XY: 0.359 AC XY: 26636 AN XY: 74148

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.344

Alfa AF: 0.373 Hom.: 10570

Bravo AF: 0.358

Asia WGS AF: 0.368 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.74

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: rs709592; hg19: chr17-38175553;