rs2563298

Variant names:

• chr5-140631730-C-A
• rs2563298
• ENST00000498971.7:c.*126G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-140631730-C-A
• chr5-140631730-C-G

Variant summary

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

The ENST00000498971.7(CD14):​c.*126G>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 866,530 control chromosomes in the GnomAD database, including 31,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5281 hom., cov: 32)
  • Exomes 𝑓: 0.26 (26117 hom.)
• Consequence: CD14 ENST00000498971.7 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 31 publications found

Genes affected

CD14 (HGNC:1628): (CD14 molecule) The protein encoded by this gene is a surface antigen that is preferentially expressed on monocytes/macrophages. It cooperates with other proteins to mediate the innate immune response to bacterial lipopolysaccharide, and to viruses. This gene has been identified as a target candidate in the treatment of SARS-CoV-2-infected patients to potentially lessen or inhibit a severe inflammatory response. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2020]

TMCO6 (HGNC:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498971.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD14	NM_000591.4	MANE Select	c.*126G>T		downstream_gene	N/A	NP_000582.1	P08571
	CD14	NM_001040021.3		c.*126G>T		downstream_gene	N/A	NP_001035110.1	P08571
	CD14	NM_001174104.2		c.*126G>T		downstream_gene	N/A	NP_001167575.1	P08571

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD14	ENST00000498971.7	TSL:2	c.*126G>T		splice_region	Exon 3 of 3	ENSP00000426543.2	P08571
	CD14	ENST00000512545.2	TSL:3	c.*126G>T		splice_region	Exon 3 of 3	ENSP00000425447.2	P08571
	CD14	ENST00000519715.2	TSL:4	c.*126G>T		splice_region	Exon 3 of 3	ENSP00000430884.2	P08571

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39290 AN: 152002 Hom.: 5282 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.263 AC: 188036 AN: 714410 Hom.: 26117 Cov.: 9 AF XY: 0.261 AC XY: 95965 AN XY: 367926

African (AFR) AF: 0.218 AC: 3927 AN: 18018

American (AMR) AF: 0.238 AC: 6467 AN: 27198

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 5053 AN: 15540

East Asian (EAS) AF: 0.160 AC: 5718 AN: 35702

South Asian (SAS) AF: 0.191 AC: 10207 AN: 53402

European-Finnish (FIN) AF: 0.319 AC: 15230 AN: 47752

Middle Eastern (MID) AF: 0.299 AC: 1061 AN: 3554

European-Non Finnish (NFE) AF: 0.275 AC: 131409 AN: 478616

Other (OTH) AF: 0.259 AC: 8964 AN: 34628

GnomAD4 genome AF: 0.258 AC: 39307 AN: 152120 Hom.: 5281 Cov.: 32 AF XY: 0.261 AC XY: 19402 AN XY: 74346

African (AFR) AF: 0.221 AC: 9161 AN: 41514

American (AMR) AF: 0.266 AC: 4068 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1104 AN: 3472

East Asian (EAS) AF: 0.145 AC: 751 AN: 5174

South Asian (SAS) AF: 0.205 AC: 985 AN: 4816

European-Finnish (FIN) AF: 0.317 AC: 3348 AN: 10564

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19143 AN: 67982

Other (OTH) AF: 0.254 AC: 535 AN: 2106

Alfa AF: 0.270 Hom.: 16730

Bravo AF: 0.250

Asia WGS AF: 0.187 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		-0.44
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2563298;

hg19: chr5-140011315;

COSMIC: COSV57370632;

COSMIC: COSV57370632;