rs2216670

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED26	NM_004831.5	c.73-4874A>C		intron_variant	Intron 1 of 2	ENST00000263390.8	NP_004822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED26	ENST00000263390.8	c.73-4874A>C		intron_variant	Intron 1 of 2	1	NM_004831.5	ENSP00000263390.3
MED26	ENST00000611692.4	c.73-4874A>C		intron_variant	Intron 1 of 3	1		ENSP00000484490.1
ENSG00000268790	ENST00000593459.5	c.116-4874A>C		intron_variant	Intron 3 of 4	3		ENSP00000470086.1
ENSG00000141979	ENST00000409035.1	n.97-4874A>C		intron_variant	Intron 2 of 11	2		ENSP00000386951.2

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

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0498

Gnomad4 EAS AF: 0.0603

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0733 Hom.: 209

Bravo AF: 0.0911

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.85

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: rs2216670; hg19: chr19-16694094;