NM_000591.4:c.*120C>G

Variant names:

• chr5-140631736-G-C
• rs3776138
• NM_000591.4:c.*120C>G

Variant summary

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

The NM_000591.4(CD14):​c.*120C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 959,734 control chromosomes in the GnomAD database, including 282 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 0.0098 (73 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (209 hom.)
• Consequence: CD14 NM_000591.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 4 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 (AMR) allele frequency at 95% confidence interval = 0.0811 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD14	NM_000591.4	MANE Select	c.*120C>G		3_prime_UTR	Exon 2 of 2	NP_000582.1
	CD14	NM_001040021.3		c.*120C>G		3_prime_UTR	Exon 3 of 3	NP_001035110.1
	CD14	NM_001174104.2		c.*120C>G		3_prime_UTR	Exon 3 of 3	NP_001167575.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD14	ENST00000302014.11	TSL:1 MANE Select	c.*120C>G		3_prime_UTR	Exon 2 of 2	ENSP00000304236.6
	CD14	ENST00000498971.7	TSL:2	c.*120C>G		3_prime_UTR	Exon 3 of 3	ENSP00000426543.2
	CD14	ENST00000512545.2	TSL:3	c.*120C>G		3_prime_UTR	Exon 3 of 3	ENSP00000425447.2

Frequencies

GnomAD3 genomes AF: 0.00969 AC: 1475 AN: 152214 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00534 AC: 4314 AN: 807402 Hom.: 209 Cov.: 11 AF XY: 0.00459 AC XY: 1889 AN XY: 411972

African (AFR) AF: 0.00228 AC: 45 AN: 19754

American (AMR) AF: 0.118 AC: 3264 AN: 27574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16240

East Asian (EAS) AF: 0.0190 AC: 688 AN: 36136

South Asian (SAS) AF: 0.000161 AC: 9 AN: 55840

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48168

Middle Eastern (MID) AF: 0.000253 AC: 1 AN: 3948

European-Non Finnish (NFE) AF: 0.000153 AC: 86 AN: 562056

Other (OTH) AF: 0.00584 AC: 220 AN: 37686

GnomAD4 genome AF: 0.00979 AC: 1491 AN: 152332 Hom.: 73 Cov.: 32 AF XY: 0.0113 AC XY: 844 AN XY: 74484

African (AFR) AF: 0.00216 AC: 90 AN: 41576

American (AMR) AF: 0.0849 AC: 1299 AN: 15300

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

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68022

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.00487 Hom.: 5

Bravo AF: 0.0171

Asia WGS AF: 0.00837 AC: 29 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	3.7
DANN	Benign	0.70
PhyloP100		-0.18
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: rs3776138; hg19: chr5-140011321;