5-140631883-C-G

Variant names:

• chr5-140631883-C-G
• rs4914
• NM_000591.4:c.1101G>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000591.4(CD14):​c.1101G>C​(p.Leu367Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,577,210 control chromosomes in the GnomAD database, including 9,188 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 0.098 (780 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8408 hom.)
• Consequence: CD14 NM_000591.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.958 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD14	NM_000591.4	c.1101G>C	p.Leu367Leu	synonymous_variant	Exon 2 of 2	ENST00000302014.11	NP_000582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000302014.11	c.1101G>C	p.Leu367Leu	synonymous_variant	Exon 2 of 2	1	NM_000591.4	ENSP00000304236.6
CD14	ENST00000498971.7	c.1101G>C	p.Leu367Leu	synonymous_variant	Exon 3 of 3	2		ENSP00000426543.2
CD14	ENST00000512545.2	c.1101G>C	p.Leu367Leu	synonymous_variant	Exon 3 of 3	3		ENSP00000425447.2
CD14	ENST00000519715.2	c.1101G>C	p.Leu367Leu	synonymous_variant	Exon 3 of 3	4		ENSP00000430884.2

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14989 AN: 152104 Hom.: 780 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0931 AC: 21515 AN: 231110 Hom.: 1198 AF XY: 0.0953 AC XY: 11830 AN XY: 124178

Gnomad AFR exome AF: 0.0725

Gnomad AMR exome AF: 0.0662

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0191

Gnomad SAS exome AF: 0.0483

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.105 AC: 150159 AN: 1424988 Hom.: 8408 Cov.: 32 AF XY: 0.104 AC XY: 73214 AN XY: 703234

Gnomad4 AFR exome AF: 0.0776

Gnomad4 AMR exome AF: 0.0672

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.0323

Gnomad4 SAS exome AF: 0.0478

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0985 AC: 14991 AN: 152222 Hom.: 780 Cov.: 32 AF XY: 0.0985 AC XY: 7328 AN XY: 74428

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.0964

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.0495

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0837 Hom.: 151

Bravo AF: 0.0955

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.8
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs4914; hg19: chr5-140011468;