rs2216670

Variant names:

• chr19-16583283-T-G
• rs2216670
• NM_004831.5:c.73-4874A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004831.5(MED26):​c.73-4874A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,298 control chromosomes in the GnomAD database, including 695 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 0.089 (695 hom., cov: 33)
• Consequence: MED26 NM_004831.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004831.5. 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
	MED26	NM_004831.5	MANE Select	c.73-4874A>C		intron	N/A	NP_004822.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED26	ENST00000263390.8	TSL:1 MANE Select	c.73-4874A>C		intron	N/A	ENSP00000263390.3
	MED26	ENST00000611692.4	TSL:1	c.73-4874A>C		intron	N/A	ENSP00000484490.1
	ENSG00000268790	ENST00000593459.5	TSL:3	c.116-4874A>C		intron	N/A	ENSP00000470086.1

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13499 AN: 152180 Hom.: 683 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0774

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0890 AC: 13558 AN: 152298 Hom.: 695 Cov.: 33 AF XY: 0.0910 AC XY: 6778 AN XY: 74470

African (AFR) AF: 0.113 AC: 4693 AN: 41558

American (AMR) AF: 0.116 AC: 1771 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 173 AN: 3472

East Asian (EAS) AF: 0.0603 AC: 312 AN: 5176

South Asian (SAS) AF: 0.0726 AC: 351 AN: 4832

European-Finnish (FIN) AF: 0.130 AC: 1377 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0681 AC: 4633 AN: 68032

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0737 Hom.: 233

Bravo AF: 0.0911

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.85
PhyloP100		-0.95
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: rs2216670; hg19: chr19-16694094;