dbSNP rs754292: MED26:c.73-10593G>A (chr19-16589002-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_004831.5(MED26):c.73-10593G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,198 control chromosomes in the GnomAD database, including 17,423 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 0.44 ( 17397 hom., cov: 32)

Exomes 𝑓: 0.51 ( 26 hom. )

Consequence

MED26
NM_004831.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

8 publications found

Variant links:

Genes affected

MED26 (HGNC:2376): (mediator complex subunit 26) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. [provided by RefSeq, Jul 2008]

MED26 links:

ENSG00000268790 (HGNC:):

ENSG00000268790 links:

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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 (SAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED26	NM_004831.5 link	c.73-10593G>A		intron_variant	Intron 1 of 2	ENST00000263390.8	NP_004822.2	O95402-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MED26	ENST00000263390.8 link	c.73-10593G>A	intron_variant	Intron 1 of 2	1	NM_004831.5	ENSP00000263390.3	O95402-1
MED26	ENST00000611692.4 link	c.73-10593G>A	intron_variant	Intron 1 of 3	1		ENSP00000484490.1	O95402-2
ENSG00000268790	ENST00000593459.5 link	c.116-10593G>A	intron_variant	Intron 3 of 4	3		ENSP00000470086.1	M0QYU9
ENSG00000141979	ENST00000409035.1 link	n.96+8428G>A	intron_variant	Intron 2 of 11	2		ENSP00000386951.2	B8ZZF3

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67309

AN:

151926

Hom.:

17399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.639

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.496

GnomAD4 exome

AF:

0.513

AC:

AN:

154

Hom.:

Cov.:

AF XY:

0.527

AC XY:

AN XY:

112

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.523

AC:

AN:

128

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.443

AC:

67316

AN:

152044

Hom.:

17397

Cov.:

AF XY:

0.446

AC XY:

33131

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.156

AC:

6486

AN:

41478

American (AMR)

AF:

0.541

AC:

8258

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

2277

AN:

3470

East Asian (EAS)

AF:

0.525

AC:

2716

AN:

5172

South Asian (SAS)

AF:

0.608

AC:

2932

AN:

4822

European-Finnish (FIN)

AF:

0.474

AC:

5009

AN:

10576

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.557

AC:

37848

AN:

67936

Other (OTH)

AF:

0.495

AC:

1048

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1684

3367

5051

6734

8418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.527

Hom.:

87633

Bravo

AF:

0.429

Asia WGS

AF:

0.540

AC:

1875

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

2.0

(source)

DANN

Benign

0.80

PhyloP100

-1.6

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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rs754292

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