chr5-140631764-A-T

Variant names:

• chr5-140631764-A-T
• rs5744456
• NM_000591.4:c.*92T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000591.4(CD14):​c.*92T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,186,312 control chromosomes in the GnomAD database, including 35 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 0.010 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (16 hom.)
• Consequence: CD14 NM_000591.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 5 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=-0.82).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1552/152326) while in subpopulation AFR AF = 0.035 (1457/41574). AF 95% confidence interval is 0.0335. There are 19 homozygotes in GnomAd4. There are 730 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD14	NM_000591.4	MANE Select	c.*92T>A		3_prime_UTR	Exon 2 of 2	NP_000582.1
	CD14	NM_001040021.3		c.*92T>A		3_prime_UTR	Exon 3 of 3	NP_001035110.1
	CD14	NM_001174104.2		c.*92T>A		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.*92T>A		3_prime_UTR	Exon 2 of 2	ENSP00000304236.6
	CD14	ENST00000498971.7	TSL:2	c.*92T>A		3_prime_UTR	Exon 3 of 3	ENSP00000426543.2
	CD14	ENST00000512545.2	TSL:3	c.*92T>A		3_prime_UTR	Exon 3 of 3	ENSP00000425447.2

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1552 AN: 152208 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00103 AC: 1068 AN: 1033986 Hom.: 16 Cov.: 13 AF XY: 0.000896 AC XY: 463 AN XY: 516550

African (AFR) AF: 0.0337 AC: 811 AN: 24058

American (AMR) AF: 0.00154 AC: 43 AN: 28010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17620

East Asian (EAS) AF: 0.00 AC: 0 AN: 37052

South Asian (SAS) AF: 0.0000330 AC: 2 AN: 60592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48824

Middle Eastern (MID) AF: 0.00386 AC: 18 AN: 4660

European-Non Finnish (NFE) AF: 0.0000885 AC: 68 AN: 767930

Other (OTH) AF: 0.00279 AC: 126 AN: 45240

GnomAD4 genome AF: 0.0102 AC: 1552 AN: 152326 Hom.: 19 Cov.: 32 AF XY: 0.00980 AC XY: 730 AN XY: 74484

African (AFR) AF: 0.0350 AC: 1457 AN: 41574

American (AMR) AF: 0.00483 AC: 74 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00707 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		0.12
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: rs5744456; hg19: chr5-140011349;