17-39416812-A-C

Variant names:

• chr17-39416812-A-C
• rs4795358
• NM_004774.4:c.1298-1473T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004774.4. 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
	MED1	NM_004774.4	MANE Select	c.1298-1473T>G		intron	N/A	NP_004765.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED1	ENST00000300651.11	TSL:1 MANE Select	c.1298-1473T>G		intron	N/A	ENSP00000300651.6	Q15648-1
	MED1	ENST00000394287.7	TSL:1	c.1298-1473T>G		intron	N/A	ENSP00000377828.3	Q15648-3
	MED1	ENST00000868127.1		c.1223-1473T>G		intron	N/A	ENSP00000538186.1

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

African (AFR) AF: 0.673 AC: 27906 AN: 41458

American (AMR) AF: 0.746 AC: 11368 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3934 AN: 5172

South Asian (SAS) AF: 0.920 AC: 4438 AN: 4824

European-Finnish (FIN) AF: 0.919 AC: 9735 AN: 10594

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56903 AN: 67994

Other (OTH) AF: 0.791 AC: 1666 AN: 2106

Alfa AF: 0.819 Hom.: 17527

Bravo AF: 0.765

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.55
PhyloP100		-0.65
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: rs4795358; hg19: chr17-37573065;