5-135576874-G-C

Variant names:

• chr5-135576874-G-C
• rs2237062
• NM_004887.5:c.170+1560C>G

Variant summary

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

The NM_004887.5(CXCL14):​c.170+1560C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,896 control chromosomes in the GnomAD database, including 5,488 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 0.27 (5488 hom., cov: 29)
• Consequence: CXCL14 NM_004887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• Publications: 7 publications found

Genes affected

CXCL14 (HGNC:10640): (C-X-C motif chemokine ligand 14) This antimicrobial gene belongs to the cytokine gene family which encode secreted proteins involved in immunoregulatory and inflammatory processes. The protein encoded by this gene is structurally related to the CXC (Cys-X-Cys) subfamily of cytokines. Members of this subfamily are characterized by two cysteines separated by a single amino acid. This cytokine displays chemotactic activity for monocytes but not for lymphocytes, dendritic cells, neutrophils or macrophages. It has been implicated that this cytokine is involved in the homeostasis of monocyte-derived macrophages rather than in inflammation. [provided by RefSeq, Sep 2014]

ENSG00000250167 (HGNC:):

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL14	NM_004887.5	c.170+1560C>G		intron_variant	Intron 2 of 3	ENST00000512158.6	NP_004878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL14	ENST00000512158.6	c.170+1560C>G		intron_variant	Intron 2 of 3	1	NM_004887.5	ENSP00000423783.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40233 AN: 151778 Hom.: 5485 Cov.: 29

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.265 AC: 40256 AN: 151896 Hom.: 5488 Cov.: 29 AF XY: 0.267 AC XY: 19787 AN XY: 74236

African (AFR) AF: 0.189 AC: 7815 AN: 41426

American (AMR) AF: 0.233 AC: 3563 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1138 AN: 3460

East Asian (EAS) AF: 0.311 AC: 1598 AN: 5146

South Asian (SAS) AF: 0.296 AC: 1423 AN: 4806

European-Finnish (FIN) AF: 0.316 AC: 3339 AN: 10568

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20402 AN: 67908

Other (OTH) AF: 0.295 AC: 622 AN: 2110

Alfa AF: 0.267 Hom.: 690

Bravo AF: 0.254

Asia WGS AF: 0.315 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.83
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: rs2237062; hg19: chr5-134912564;