ENST00000524289.1:c.-258+1511G>A

Variant names:

• chr5-157157373-C-T
• rs246869
• ENST00000524289.1:c.-258+1511G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000524289.1(MED7):​c.-258+1511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,108 control chromosomes in the GnomAD database, including 1,355 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 0.13 (1355 hom., cov: 31)
• Consequence: MED7 ENST00000524289.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED7	ENST00000524289.1	c.-258+1511G>A		intron_variant	Intron 1 of 2	3		ENSP00000430746.1
ITK	ENST00000521769.5	c.-296-8715C>T		intron_variant	Intron 1 of 6	4		ENSP00000430327.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19213 AN: 151990 Hom.: 1353 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.126 AC: 19226 AN: 152108 Hom.: 1355 Cov.: 31 AF XY: 0.120 AC XY: 8949 AN XY: 74370

African (AFR) AF: 0.166 AC: 6874 AN: 41462

American (AMR) AF: 0.0901 AC: 1378 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3466

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5184

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4822

European-Finnish (FIN) AF: 0.0902 AC: 953 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8937 AN: 67992

Other (OTH) AF: 0.120 AC: 253 AN: 2114

Alfa AF: 0.140 Hom.: 194

Bravo AF: 0.128

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs246869; hg19: chr5-156584384;