17-40019300-C-T

Variant names:

• chr17-40019300-C-T
• rs709592
• NM_014815.4:c.*229G>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.*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
• Publications: 38 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED24	NM_014815.4	MANE Select	c.*229G>A		3_prime_UTR	Exon 26 of 26	NP_055630.2
	MED24	NM_001330211.2		c.*229G>A		3_prime_UTR	Exon 27 of 27	NP_001317140.1
	MED24	NM_001079518.2		c.*229G>A		3_prime_UTR	Exon 25 of 25	NP_001072986.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED24	ENST00000394128.7	TSL:1 MANE Select	c.*229G>A		3_prime_UTR	Exon 26 of 26	ENSP00000377686.2
	MED24	ENST00000394126.5	TSL:1	c.*229G>A		3_prime_UTR	Exon 25 of 25	ENSP00000377684.1
	MED24	ENST00000887917.1		c.*229G>A		3_prime_UTR	Exon 27 of 27	ENSP00000557976.1

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

African (AFR) AF: 0.316 AC: 3419 AN: 10824

American (AMR) AF: 0.333 AC: 4752 AN: 14250

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 4261 AN: 12414

East Asian (EAS) AF: 0.428 AC: 11562 AN: 26994

South Asian (SAS) AF: 0.256 AC: 10486 AN: 40912

European-Finnish (FIN) AF: 0.394 AC: 10554 AN: 26792

Middle Eastern (MID) AF: 0.245 AC: 441 AN: 1798

European-Non Finnish (NFE) AF: 0.384 AC: 92515 AN: 241060

Other (OTH) AF: 0.374 AC: 8720 AN: 23302

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

African (AFR) AF: 0.315 AC: 13013 AN: 41346

American (AMR) AF: 0.349 AC: 5330 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1200 AN: 3456

East Asian (EAS) AF: 0.439 AC: 2251 AN: 5132

South Asian (SAS) AF: 0.258 AC: 1242 AN: 4816

European-Finnish (FIN) AF: 0.393 AC: 4147 AN: 10542

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26489 AN: 67860

Other (OTH) AF: 0.344 AC: 728 AN: 2116

Alfa AF: 0.373 Hom.: 26102

Bravo AF: 0.358

Asia WGS AF: 0.368 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.74
PhyloP100		0.51
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: rs709592; hg19: chr17-38175553;