5-140633331-A-G

Variant names:

• chr5-140633331-A-G
• rs2569190
• NM_001040021.3:c.-121-139T>C

Variant summary

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

The NM_001040021.3(CD14):​c.-121-139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 598,992 control chromosomes in the GnomAD database, including 86,070 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 0.57 (24871 hom., cov: 31)
  • Exomes 𝑓: 0.52 (61199 hom.)
• Consequence: CD14 NM_001040021.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 618 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040021.3. 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_001040021.3		c.-121-139T>C		intron	N/A	NP_001035110.1
	CD14	NM_001174104.2		c.-221-39T>C		intron	N/A	NP_001167575.1
	CD14	NM_001174105.2		c.-121-139T>C		intron	N/A	NP_001167576.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD14	ENST00000498971.7	TSL:2	c.-121-139T>C		intron	N/A	ENSP00000426543.2
	CD14	ENST00000512545.2	TSL:3	c.-221-39T>C		intron	N/A	ENSP00000425447.2
	CD14	ENST00000519715.2	TSL:4	c.-121-139T>C		intron	N/A	ENSP00000430884.2

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85846 AN: 151726 Hom.: 24820 Cov.: 31

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.520 AC: 232594 AN: 447148 Hom.: 61199 Cov.: 4 AF XY: 0.515 AC XY: 121968 AN XY: 237050

African (AFR) AF: 0.660 AC: 8348 AN: 12656

American (AMR) AF: 0.507 AC: 10712 AN: 21142

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 7329 AN: 13844

East Asian (EAS) AF: 0.448 AC: 13453 AN: 30012

South Asian (SAS) AF: 0.449 AC: 21493 AN: 47902

European-Finnish (FIN) AF: 0.615 AC: 17213 AN: 27980

Middle Eastern (MID) AF: 0.493 AC: 943 AN: 1914

European-Non Finnish (NFE) AF: 0.524 AC: 139523 AN: 266088

Other (OTH) AF: 0.530 AC: 13580 AN: 25610

GnomAD4 genome AF: 0.566 AC: 85953 AN: 151844 Hom.: 24871 Cov.: 31 AF XY: 0.568 AC XY: 42170 AN XY: 74194

African (AFR) AF: 0.672 AC: 27828 AN: 41384

American (AMR) AF: 0.530 AC: 8088 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1833 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2282 AN: 5152

South Asian (SAS) AF: 0.467 AC: 2250 AN: 4820

European-Finnish (FIN) AF: 0.626 AC: 6582 AN: 10518

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35625 AN: 67918

Other (OTH) AF: 0.547 AC: 1154 AN: 2110

Alfa AF: 0.531 Hom.: 34727

Bravo AF: 0.559

Asia WGS AF: 0.524 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.46
PhyloP100		-1.1
PromoterAI		0.15	Neutral
Mutation Taster		=297/3	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: rs2569190; hg19: chr5-140012916; COSMIC: COSV57371477;