4-73998833-G-C

Variant names:

• chr4-73998833-G-C
• rs352046
• ENST00000769990.1:n.214G>C

Variant summary

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

The ENST00000769990.1(ENSG00000287037):​n.214G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 555,290 control chromosomes in the GnomAD database, including 206,409 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 0.80 (50049 hom., cov: 31)
  • Exomes 𝑓: 0.88 (156360 hom.)
• Consequence: ENSG00000287037 ENST00000769990.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 28 publications found

Genes affected

ENSG00000287037 (HGNC:58815):

LOC124900715 (HGNC:):

CXCL5 (HGNC:10642): (C-X-C motif chemokine ligand 5) This gene encodes a protein that is a member of the CXC subfamily of chemokines. Chemokines, which recruit and activate leukocytes, are classified by function (inflammatory or homeostatic) or by structure. This protein is proposed to bind the G-protein coupled receptor chemokine (C-X-C motif) receptor 2 to recruit neutrophils, to promote angiogenesis and to remodel connective tissues. This protein is thought to play a role in cancer cell proliferation, migration, and invasion. [provided by RefSeq, May 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900715	XR_007058140.1	n.606G>C		non_coding_transcript_exon_variant	Exon 1 of 2
CXCL5	NM_002994.5	c.-252C>G		upstream_gene_variant		ENST00000296027.5	NP_002985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL5	ENST00000296027.5	c.-252C>G		upstream_gene_variant		1	NM_002994.5	ENSP00000296027.4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121717 AN: 152020 Hom.: 50045 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.878 AC: 353902 AN: 403152 Hom.: 156360 AF XY: 0.877 AC XY: 186842 AN XY: 213030

African (AFR) AF: 0.590 AC: 6346 AN: 10752

American (AMR) AF: 0.878 AC: 12875 AN: 14664

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 10534 AN: 12236

East Asian (EAS) AF: 0.977 AC: 26519 AN: 27130

South Asian (SAS) AF: 0.859 AC: 35907 AN: 41798

European-Finnish (FIN) AF: 0.898 AC: 24011 AN: 26748

Middle Eastern (MID) AF: 0.838 AC: 1464 AN: 1746

European-Non Finnish (NFE) AF: 0.884 AC: 216429 AN: 244938

Other (OTH) AF: 0.856 AC: 19817 AN: 23140

GnomAD4 genome AF: 0.800 AC: 121752 AN: 152138 Hom.: 50049 Cov.: 31 AF XY: 0.804 AC XY: 59799 AN XY: 74382

African (AFR) AF: 0.591 AC: 24530 AN: 41506

American (AMR) AF: 0.870 AC: 13294 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2979 AN: 3472

East Asian (EAS) AF: 0.968 AC: 4987 AN: 5150

South Asian (SAS) AF: 0.867 AC: 4169 AN: 4810

European-Finnish (FIN) AF: 0.877 AC: 9311 AN: 10612

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59640 AN: 67988

Other (OTH) AF: 0.814 AC: 1715 AN: 2108

Alfa AF: 0.812 Hom.: 2765

Bravo AF: 0.789

Asia WGS AF: 0.848 AC: 2948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.50
PhyloP100		0.43
PromoterAI		0.050	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs352046; hg19: chr4-74864550;