19-16624977-C-T

Position:

• chr19-16624977-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.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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MED26	NM_004831.5	c.72+2895G>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.72+2895G>A		intron_variant		1	NM_004831.5	ENSP00000263390	P1
	ENST00000597226.1	n.28-11206C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.0629

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0634

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.0596 Hom.: 143

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

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: rs3786603; hg19: chr19-16735788;