rs4795358

chr17-39416812-A-Cchr17-39416812-A-Gchr17-39416812-A-T

Variant summary

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

The NM_004774.4(MED1):c.1298-1473T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,072 control chromosomes in the GnomAD database, including 47,502 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 0.79 (47502 hom., cov: 32)
• Consequence: MED1 NM_004774.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

Genes affected

MED1 (HGNC:9234): (mediator complex subunit 1) 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. It also regulates p53-dependent apoptosis and it is essential for adipogenesis. This protein is known to have the ability to self-oligomerize. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED1	NM_004774.4	c.1298-1473T>G		intron_variant		ENST00000300651.11
MED1	XM_006721957.3	c.1298-1473T>G		intron_variant
MED1	XM_047436314.1	c.782-1473T>G		intron_variant
MED1	XM_047436315.1	c.641-1473T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED1	ENST00000300651.11	c.1298-1473T>G		intron_variant		1	NM_004774.4	P1
MED1	ENST00000394287.7	c.1298-1473T>G		intron_variant		1
MED1	ENST00000577831.5	c.*871-1473T>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119434 AN: 151954 Hom.: 47461 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.786 AC: 119539 AN: 152072 Hom.: 47502 Cov.: 32 AF XY: 0.789 AC XY: 58681 AN XY: 74348

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.791

Alfa AF: 0.825 Hom.: 10555

Bravo AF: 0.765

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.7
Dann	Benign	0.55

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: rs4795358; hg19: chr17-37573065;