chr5-140631883-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_000591.4(CD14):​c.1101G>T​(p.Leu367Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,425,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CD14 NM_000591.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958
• Publications: 42 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.958 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000591.4. 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.1101G>T	p.Leu367Leu	synonymous	Exon 2 of 2	NP_000582.1	P08571
	CD14	NM_001040021.3		c.1101G>T	p.Leu367Leu	synonymous	Exon 3 of 3	NP_001035110.1	P08571
	CD14	NM_001174104.2		c.1101G>T	p.Leu367Leu	synonymous	Exon 3 of 3	NP_001167575.1	P08571

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD14	ENST00000302014.11	TSL:1 MANE Select	c.1101G>T	p.Leu367Leu	synonymous	Exon 2 of 2	ENSP00000304236.6	P08571
	CD14	ENST00000498971.7	TSL:2	c.1101G>T	p.Leu367Leu	synonymous	Exon 3 of 3	ENSP00000426543.2	P08571
	CD14	ENST00000512545.2	TSL:3	c.1101G>T	p.Leu367Leu	synonymous	Exon 3 of 3	ENSP00000425447.2	P08571

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000476 AC: 11 AN: 231110 AF XY: 0.0000403

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000342

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000112 AC: 16 AN: 1425234 Hom.: 0 Cov.: 32 AF XY: 0.00000853 AC XY: 6 AN XY: 703374

African (AFR) AF: 0.00 AC: 0 AN: 32754

American (AMR) AF: 0.000262 AC: 11 AN: 42012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23742

East Asian (EAS) AF: 0.00 AC: 0 AN: 39124

South Asian (SAS) AF: 0.00 AC: 0 AN: 81948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00000459 AC: 5 AN: 1089196

Other (OTH) AF: 0.00 AC: 0 AN: 58676

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 151

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.7
DANN	Benign	0.39
PhyloP100		0.96

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: rs4914; hg19: chr5-140011468;