rs77083413

Variant names:

• chr5-140631967-G-C
• rs77083413
• NM_000591.4:c.1017C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_000591.4(CD14):​c.1017C>G​(p.Pro339Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000793 in 1,613,710 control chromosomes in the GnomAD database, including 18 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 0.00062 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (16 hom.)
• Consequence: CD14 NM_000591.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 3 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=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.44 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000812 (1186/1461424) while in subpopulation EAS AF = 0.0242 (961/39680). AF 95% confidence interval is 0.0229. There are 16 homozygotes in GnomAdExome4. There are 623 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.1017C>G	p.Pro339Pro	synonymous	Exon 2 of 2	NP_000582.1	P08571
	CD14	NM_001040021.3		c.1017C>G	p.Pro339Pro	synonymous	Exon 3 of 3	NP_001035110.1	P08571
	CD14	NM_001174104.2		c.1017C>G	p.Pro339Pro	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.1017C>G	p.Pro339Pro	synonymous	Exon 2 of 2	ENSP00000304236.6	P08571
	CD14	ENST00000498971.7	TSL:2	c.1017C>G	p.Pro339Pro	synonymous	Exon 3 of 3	ENSP00000426543.2	P08571
	CD14	ENST00000512545.2	TSL:3	c.1017C>G	p.Pro339Pro	synonymous	Exon 3 of 3	ENSP00000425447.2	P08571

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152168 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000988 AC: 248 AN: 251022 AF XY: 0.00101

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.000812 AC: 1186 AN: 1461424 Hom.: 16 Cov.: 32 AF XY: 0.000857 AC XY: 623 AN XY: 726944

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0242 AC: 961 AN: 39680

South Asian (SAS) AF: 0.000557 AC: 48 AN: 86246

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53400

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1111632

Other (OTH) AF: 0.000662 AC: 40 AN: 60378

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152286 Hom.: 2 Cov.: 32 AF XY: 0.000739 AC XY: 55 AN XY: 74458

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5180

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000446

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs77083413; hg19: chr5-140011552;