Genetic Variant NM_014815.4:c.*229G>A (chr17-40019300-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.512

Publications

38 publications found

Variant links:

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]

MED24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED24	NM_014815.4 link	c.*229G>A		3_prime_UTR_variant	Exon 26 of 26	ENST00000394128.7	NP_055630.2	O75448-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED24	ENST00000394128.7 link	c.*229G>A		3_prime_UTR_variant	Exon 26 of 26	1	NM_014815.4	ENSP00000377686.2		O75448-1

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54783

AN:

151614

Hom.:

9942

Cov.:

show subpopulations

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.:

AF XY:

0.361

AC XY:

75527

AN XY:

209184

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4158

8316

12474

16632

20790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.362

AC:

54861

AN:

151732

Hom.:

9960

Cov.:

AF XY:

0.359

AC XY:

26636

AN XY:

74148

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26489

AN:

67860

Other (OTH)

AF:

0.344

AC:

728

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1776

3553

5329

7106

8882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.2

(source)

DANN

Benign

0.74

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over