chr5-157158243-T-C

Variant names:

• chr5-157158243-T-C
• rs246871
• ENST00000524289.1:c.-258+641A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ITK Gene-Disease associations (from GenCC):

• lymphoproliferative syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• lymphoproliferative syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524289.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED7	ENST00000524289.1	TSL:3	c.-258+641A>G		intron	N/A	ENSP00000430746.1
	ITK	ENST00000521769.5	TSL:4	c.-296-7845T>C		intron	N/A	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

African (AFR) AF: 0.661 AC: 27380 AN: 41418

American (AMR) AF: 0.317 AC: 4841 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 914 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1121 AN: 5168

South Asian (SAS) AF: 0.300 AC: 1449 AN: 4822

European-Finnish (FIN) AF: 0.264 AC: 2799 AN: 10598

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23291 AN: 67990

Other (OTH) AF: 0.396 AC: 834 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.67
PhyloP100		-0.020

Splicing

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

Other links and lift over

dbSNP: rs246871; hg19: chr5-156585254;