chr17-40025976-G-T

Variant names:

• chr17-40025976-G-T
• rs9916158
• NM_014815.4:c.1985+180C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014815.4(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 NM_014815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014815.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED24	NM_014815.4	MANE Select	c.1985+180C>A		intron	N/A	NP_055630.2
	MED24	NM_001330211.2		c.2042+180C>A		intron	N/A	NP_001317140.1
	MED24	NM_001079518.2		c.1946+180C>A		intron	N/A	NP_001072986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED24	ENST00000394128.7	TSL:1 MANE Select	c.1985+180C>A		intron	N/A	ENSP00000377686.2
	MED24	ENST00000394126.5	TSL:1	c.2060+180C>A		intron	N/A	ENSP00000377684.1
	MED24	ENST00000501516.7	TSL:5	c.2042+180C>A		intron	N/A	ENSP00000440100.2

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

African (AFR) AF: 0.240 AC: 9941 AN: 41462

American (AMR) AF: 0.412 AC: 6293 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1448 AN: 3472

East Asian (EAS) AF: 0.413 AC: 2131 AN: 5160

South Asian (SAS) AF: 0.472 AC: 2272 AN: 4816

European-Finnish (FIN) AF: 0.323 AC: 3410 AN: 10570

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25574 AN: 67988

Other (OTH) AF: 0.384 AC: 812 AN: 2112

Alfa AF: 0.368 Hom.: 18020

Bravo AF: 0.349

Asia WGS AF: 0.420 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.69
PhyloP100		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9916158; hg19: chr17-38182229;