chr4-76034048-A-G

Variant names:

• chr4-76034048-A-G
• rs4619915
• NM_005409.5:c.*745T>C

Variant summary

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

The NM_005409.5(CXCL11):​c.*745T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,722 control chromosomes in the GnomAD database, including 29,330 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 0.61 (29330 hom., cov: 33)
  • Exomes 𝑓: 0.54 (1776 hom.)
  • Failed GnomAD Quality Control
• Consequence: CXCL11 NM_005409.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 21 publications found

Genes affected

CXCL11 (HGNC:10638): (C-X-C motif chemokine ligand 11) Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC. This antimicrobial gene is a CXC member of the chemokine superfamily. Its encoded protein induces a chemotactic response in activated T-cells and is the dominant ligand for CXC receptor-3. The gene encoding this protein contains 4 exons and at least three polyadenylation signals which might reflect cell-specific regulation of expression. IFN-gamma is a potent inducer of transcription of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

ART3 (HGNC:725): (ADP-ribosyltransferase 3 (inactive)) This gene encodes an arginine-specific ADP-ribosyltransferase. The encoded protein catalyzes a reversible reaction which modifies proteins by the addition or removal of ADP-ribose to an arginine residue to regulate the function of the modified protein. An ADP-ribosyltransferase pseudogene is located on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL11	NM_005409.5	c.*745T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000306621.8	NP_005400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL11	ENST00000306621.8	c.*745T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_005409.5	ENSP00000306884.3

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92529 AN: 151604 Hom.: 29278 Cov.: 33

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.621

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.537 AC: 6289 AN: 11718 Hom.: 1776 Cov.: 0 AF XY: 0.525 AC XY: 3140 AN XY: 5980

African (AFR) AF: 0.674 AC: 349 AN: 518

American (AMR) AF: 0.707 AC: 222 AN: 314

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 346 AN: 598

East Asian (EAS) AF: 0.927 AC: 614 AN: 662

South Asian (SAS) AF: 0.528 AC: 57 AN: 108

European-Finnish (FIN) AF: 0.438 AC: 190 AN: 434

Middle Eastern (MID) AF: 0.545 AC: 36 AN: 66

European-Non Finnish (NFE) AF: 0.488 AC: 3981 AN: 8154

Other (OTH) AF: 0.572 AC: 494 AN: 864

GnomAD4 genome AF: 0.611 AC: 92645 AN: 151722 Hom.: 29330 Cov.: 33 AF XY: 0.610 AC XY: 45245 AN XY: 74130

African (AFR) AF: 0.704 AC: 29131 AN: 41396

American (AMR) AF: 0.717 AC: 10925 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3468

East Asian (EAS) AF: 0.938 AC: 4846 AN: 5166

South Asian (SAS) AF: 0.549 AC: 2649 AN: 4824

European-Finnish (FIN) AF: 0.468 AC: 4907 AN: 10482

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 35992 AN: 67832

Other (OTH) AF: 0.622 AC: 1309 AN: 2106

Alfa AF: 0.587 Hom.: 3692

Bravo AF: 0.640

Asia WGS AF: 0.719 AC: 2496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.41
PhyloP100		0.14
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: rs4619915; hg19: chr4-76955201;