5-140631883-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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.

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>C	p.Leu367Leu	synonymous	Exon 2 of 2	NP_000582.1	P08571
	CD14	NM_001040021.3		c.1101G>C	p.Leu367Leu	synonymous	Exon 3 of 3	NP_001035110.1	P08571
	CD14	NM_001174104.2		c.1101G>C	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>C	p.Leu367Leu	synonymous	Exon 2 of 2	ENSP00000304236.6	P08571
	CD14	ENST00000498971.7	TSL:2	c.1101G>C	p.Leu367Leu	synonymous	Exon 3 of 3	ENSP00000426543.2	P08571
	CD14	ENST00000512545.2	TSL:3	c.1101G>C	p.Leu367Leu	synonymous	Exon 3 of 3	ENSP00000425447.2	P08571

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

GnomAD2 exomes AF: 0.0931 AC: 21515 AN: 231110 AF XY: 0.0953

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 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

African (AFR) AF: 0.0776 AC: 2542 AN: 32754

American (AMR) AF: 0.0672 AC: 2822 AN: 41998

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3497 AN: 23736

East Asian (EAS) AF: 0.0323 AC: 1264 AN: 39118

South Asian (SAS) AF: 0.0478 AC: 3919 AN: 81932

European-Finnish (FIN) AF: 0.124 AC: 6473 AN: 52196

Middle Eastern (MID) AF: 0.156 AC: 871 AN: 5580

European-Non Finnish (NFE) AF: 0.113 AC: 122627 AN: 1089012

Other (OTH) AF: 0.105 AC: 6144 AN: 58662

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

African (AFR) AF: 0.0761 AC: 3161 AN: 41532

American (AMR) AF: 0.0964 AC: 1474 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3472

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5176

South Asian (SAS) AF: 0.0495 AC: 239 AN: 4828

European-Finnish (FIN) AF: 0.126 AC: 1332 AN: 10600

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.116 AC: 7855 AN: 68004

Other (OTH) AF: 0.100 AC: 212 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.8
DANN	Benign	0.37
PhyloP100		0.96
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: rs4914; hg19: chr5-140011468;