19-16624977-C-T

Variant names:

• chr19-16624977-C-T
• rs3786603
• NM_004831.5:c.72+2895G>A

Variant summary

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

The NM_004831.5(MED26):​c.72+2895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 152,234 control chromosomes in the GnomAD database, including 281 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 0.051 (281 hom., cov: 32)
• Consequence: MED26 NM_004831.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED26	NM_004831.5	c.72+2895G>A		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.72+2895G>A		intron_variant	Intron 1 of 2	1	NM_004831.5	ENSP00000263390.3
MED26	ENST00000611692.4	c.72+2895G>A		intron_variant	Intron 1 of 3	1		ENSP00000484490.1
ENSG00000268790	ENST00000593459.5	c.115+34418G>A		intron_variant	Intron 3 of 4	3		ENSP00000470086.1
ENSG00000141979	ENST00000409035.1	n.72+2895G>A		intron_variant	Intron 1 of 11	2		ENSP00000386951.2

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7828 AN: 152116 Hom.: 281 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0514 AC: 7832 AN: 152234 Hom.: 281 Cov.: 32 AF XY: 0.0539 AC XY: 4010 AN XY: 74414

African (AFR) AF: 0.0249 AC: 1035 AN: 41540

American (AMR) AF: 0.0267 AC: 409 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3468

East Asian (EAS) AF: 0.0270 AC: 140 AN: 5194

South Asian (SAS) AF: 0.0629 AC: 303 AN: 4818

European-Finnish (FIN) AF: 0.126 AC: 1337 AN: 10582

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0634 AC: 4310 AN: 68014

Other (OTH) AF: 0.0351 AC: 74 AN: 2110

Alfa AF: 0.0597 Hom.: 158

Bravo AF: 0.0422

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.50
PromoterAI		0.028	Neutral
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: rs3786603; hg19: chr19-16735788;