rs8065443

Positions:

• chr17-40052687-A-G

Variant summary

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

The NM_014815.4(MED24):​c.213+611T>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 151,968 control chromosomes in the GnomAD database, including 29,165 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 (29165 hom., cov: 31)
• Consequence: MED24 NM_014815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED24	NM_014815.4	c.213+611T>C		intron_variant		ENST00000394128.7	NP_055630.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7	c.213+611T>C		intron_variant		1	NM_014815.4	ENSP00000377686	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93785 AN: 151850 Hom.: 29145 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.618 AC: 93849 AN: 151968 Hom.: 29165 Cov.: 31 AF XY: 0.620 AC XY: 46036 AN XY: 74260

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.638

Alfa AF: 0.589 Hom.: 3347

Bravo AF: 0.628

Asia WGS AF: 0.628 AC: 2186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.21

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: rs8065443; hg19: chr17-38208940;