rs2569190

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-140633331-A-C
• chr5-140633331-A-G
• chr5-140633331-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040021.3(CD14):​c.-121-139T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 447,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD14	NM_000591.4	c.-260T>G		upstream_gene_variant		ENST00000302014.11	NP_000582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000498971.7	c.-121-139T>G		intron_variant	Intron 1 of 2	2		ENSP00000426543.2
CD14	ENST00000512545.2	c.-221-39T>G		intron_variant	Intron 1 of 2	3		ENSP00000425447.2
CD14	ENST00000519715.2	c.-121-139T>G		intron_variant	Intron 1 of 2	4		ENSP00000430884.2
CD14	ENST00000302014.11	c.-260T>G		upstream_gene_variant		1	NM_000591.4	ENSP00000304236.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000223 AC: 1 AN: 447840 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 237434

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12672

American (AMR) AF: 0.00 AC: 0 AN: 21172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13874

East Asian (EAS) AF: 0.00 AC: 0 AN: 30050

South Asian (SAS) AF: 0.00 AC: 0 AN: 47938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1914

European-Non Finnish (NFE) AF: 0.00000375 AC: 1 AN: 266528

Other (OTH) AF: 0.00 AC: 0 AN: 25662

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.92
DANN	Benign	0.45
PhyloP100		-1.1
PromoterAI		0.065	Neutral

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;