chr5-140631736-G-C

Position:

• chr5-140631736-G-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD14	NM_000591.4	c.*120C>G		3_prime_UTR_variant	2/2	ENST00000302014.11	NP_000582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000302014.11	c.*120C>G		3_prime_UTR_variant	2/2	1	NM_000591.4	ENSP00000304236	P1
CD14	ENST00000498971.7	c.*120C>G		3_prime_UTR_variant	3/3	2		ENSP00000426543	P1
CD14	ENST00000512545.2	c.*120C>G		3_prime_UTR_variant	3/3	3		ENSP00000425447	P1
CD14	ENST00000519715.2	c.*120C>G		3_prime_UTR_variant	3/3	4		ENSP00000430884	P1

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

Gnomad4 AFR exome AF: 0.00228

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.0000208

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00584

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

Gnomad4 AFR AF: 0.00216

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0128

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.7
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs3776138; hg19: chr5-140011321;