Genetic Variant MED28:c.*10139_*10143delATAAA (chr4-17633933-CAAAAT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_025205.5(MED28):c.*10139_*10143delATAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,327,290 control chromosomes in the GnomAD database, including 238,215 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 23001 hom., cov: 0)

Exomes 𝑓: 0.60 ( 215214 hom. )

Consequence

MED28
NM_025205.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Publications

8 publications found

Variant links:

Genes affected

MED28 (HGNC:24628): (mediator complex subunit 28) Predicted to enable actin binding activity. Predicted to act upstream of or within negative regulation of smooth muscle cell differentiation and stem cell population maintenance. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MED28 links:

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

FAM184B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MED28	NM_025205.5 link	c.10139_10143delATAAA	3_prime_UTR_variant	Exon 4 of 4	ENST00000237380.12	NP_079481.2	Q9H204
FAM184B	NM_015688.2 link	c.2890-50_2890-46delATTTT	intron_variant	Intron 16 of 17	ENST00000265018.4	NP_056503.1	Q9ULE4
FAM184B	XM_047450066.1 link	c.2890-50_2890-46delATTTT	intron_variant	Intron 16 of 16		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED28	ENST00000237380.12 link	c.10139_10143delATAAA		3_prime_UTR_variant	Exon 4 of 4	1	NM_025205.5	ENSP00000237380.6		Q9H204
FAM184B	ENST00000265018.4 link	c.2890-50_2890-46delATTTT		intron_variant	Intron 16 of 17	1	NM_015688.2	ENSP00000265018.3		Q9ULE4

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77670

AN:

151504

Hom.:

22990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.526

Gnomad EAS

AF:

0.880

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.680

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.537

GnomAD2 exomes

AF:

0.615

AC:

32944

AN:

53556

AF XY:

0.610

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.501

Gnomad EAS exome

AF:

0.893

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.598

AC:

702549

AN:

1175666

Hom.:

215214

AF XY:

0.598

AC XY:

340115

AN XY:

569026

show subpopulations

African (AFR)

AF:

0.182

AC:

4479

AN:

24580

American (AMR)

AF:

0.688

AC:

9471

AN:

13758

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

8559

AN:

17182

East Asian (EAS)

AF:

0.904

AC:

26401

AN:

29218

South Asian (SAS)

AF:

0.561

AC:

26043

AN:

46438

European-Finnish (FIN)

AF:

0.687

AC:

28847

AN:

42014

Middle Eastern (MID)

AF:

0.573

AC:

2305

AN:

4022

European-Non Finnish (NFE)

AF:

0.598

AC:

568493

AN:

950898

Other (OTH)

AF:

0.588

AC:

27951

AN:

47556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

13012

26025

39037

52050

65062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16730

33460

50190

66920

83650

<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:

0.512

AC:

77695

AN:

151624

Hom.:

23001

Cov.:

AF XY:

0.519

AC XY:

38451

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.205

AC:

8486

AN:

41464

American (AMR)

AF:

0.650

AC:

9875

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

1821

AN:

3462

East Asian (EAS)

AF:

0.880

AC:

4518

AN:

5134

South Asian (SAS)

AF:

0.548

AC:

2638

AN:

4810

European-Finnish (FIN)

AF:

0.680

AC:

7123

AN:

10468

Middle Eastern (MID)

AF:

0.599

AC:

175

AN:

292

European-Non Finnish (NFE)

AF:

0.611

AC:

41415

AN:

67780

Other (OTH)

AF:

0.541

AC:

1142

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1607

3214

4820

6427

8034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.539

Hom.:

4160

Bravo

AF:

0.500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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