rs3733910

Positions:

• chr5-67183361-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005582.3(CD180):​c.1482C>T​(p.Thr494Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,614,062 control chromosomes in the GnomAD database, including 2,278 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 0.075 (1126 hom., cov: 32)
  • Exomes 𝑓: 0.018 (1152 hom.)
• Consequence: CD180 NM_005582.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

Genes affected

CD180 (HGNC:6726): (CD180 molecule) CD180 is a cell surface molecule consisting of extracellular leucine-rich repeats (LRR) and a short cytoplasmic tail. The extracellular LRR is associated with a molecule called MD-1 and form the cell surface receptor complex, RP105/MD-1. It belongs to the family of pathogen receptors, Toll-like receptors (TLR). RP105/MD1, by working in concert with TLR4, controls B cell recognition and signaling of lipopolysaccharide (LPS), a membrane constituent of Gram-negative bacteria. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-3.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD180	NM_005582.3	c.1482C>T	p.Thr494Thr	synonymous_variant	3/3	ENST00000256447.5	NP_005573.2
CD180	XM_005248504.5	c.1443C>T	p.Thr481Thr	synonymous_variant	4/4		XP_005248561.1
CD180	XM_047417178.1	c.1443C>T	p.Thr481Thr	synonymous_variant	4/4		XP_047273134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD180	ENST00000256447.5	c.1482C>T	p.Thr494Thr	synonymous_variant	3/3	1	NM_005582.3	ENSP00000256447.4

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11393 AN: 152068 Hom.: 1125 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00932

Gnomad OTH AF: 0.0537

GnomAD3 exomes AF: 0.0304 AC: 7648 AN: 251382 Hom.: 513 AF XY: 0.0270 AC XY: 3670 AN XY: 135860

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.0164

Gnomad ASJ exome AF: 0.00725

Gnomad EAS exome AF: 0.0310

Gnomad SAS exome AF: 0.0273

Gnomad FIN exome AF: 0.0264

Gnomad NFE exome AF: 0.00943

Gnomad OTH exome AF: 0.0197

GnomAD4 exome AF: 0.0175 AC: 25627 AN: 1461876 Hom.: 1152 Cov.: 33 AF XY: 0.0170 AC XY: 12380 AN XY: 727240

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.00792

Gnomad4 EAS exome AF: 0.0296

Gnomad4 SAS exome AF: 0.0268

Gnomad4 FIN exome AF: 0.0268

Gnomad4 NFE exome AF: 0.00893

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.0749 AC: 11406 AN: 152186 Hom.: 1126 Cov.: 32 AF XY: 0.0747 AC XY: 5558 AN XY: 74410

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.00932

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0251 Hom.: 368

Bravo AF: 0.0821

Asia WGS AF: 0.0550 AC: 192 AN: 3478

EpiCase AF: 0.00932

EpiControl AF: 0.0101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.29

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: rs3733910; hg19: chr5-66479189;