rs246871

Positions:

• chr5-157158243-T-C

Variant summary

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

The ENST00000524289.1(MED7):​c.-258+641A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,036 control chromosomes in the GnomAD database, including 14,983 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 0.41 (14983 hom., cov: 32)
• Consequence: MED7 ENST00000524289.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

Genes affected

MED7 (HGNC:2378): (mediator complex subunit 7) 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. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ITK (HGNC:6171): (IL2 inducible T cell kinase) This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.157158243T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED7	ENST00000524289.1	c.-258+641A>G		intron_variant		3		ENSP00000430746.1
ITK	ENST00000521769.5	c.-296-7845T>C		intron_variant		4		ENSP00000430327.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62895 AN: 151918 Hom.: 14936 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.414 AC: 62987 AN: 152036 Hom.: 14983 Cov.: 32 AF XY: 0.407 AC XY: 30259 AN XY: 74362

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.396

Alfa AF: 0.390 Hom.: 2141

Bravo AF: 0.427

Asia WGS AF: 0.271 AC: 943 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	3.9
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs246871; hg19: chr5-156585254;