rs754292

Positions:

• chr19-16589002-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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]

ENSG00000268790 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MED26	NM_004831.5	c.73-10593G>A		intron_variant		ENST00000263390.8	NP_004822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED26	ENST00000263390.8	c.73-10593G>A		intron_variant		1	NM_004831.5	ENSP00000263390.3
MED26	ENST00000611692.4	c.73-10593G>A		intron_variant		1		ENSP00000484490.1
ENSG00000268790	ENST00000593459.5	c.116-10593G>A		intron_variant		3		ENSP00000470086.1
ENSG00000141979	ENST00000409035.1	n.96+8428G>A		intron_variant		2		ENSP00000386951.2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67309 AN: 151926 Hom.: 17399 Cov.: 32

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: 79 AN: 154 Hom.: 26 Cov.: 0 AF XY: 0.527 AC XY: 59 AN XY: 112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.443 AC: 67316 AN: 152044 Hom.: 17397 Cov.: 32 AF XY: 0.446 AC XY: 33131 AN XY: 74336

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.495

Alfa AF: 0.548 Hom.: 37880

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
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs754292; hg19: chr19-16699813;