rs2230524

Variant names:

• chr5-67182901-A-G
• rs2230524
• NM_005582.3:c.1942T>C

Variant summary

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

The NM_005582.3(CD180):​c.1942T>C​(p.Phe648Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,612,622 control chromosomes in the GnomAD database, including 3,415 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.054 (464 hom., cov: 32)
  • Exomes 𝑓: 0.032 (2951 hom.)
• Consequence: CD180 NM_005582.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042049885).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD180	NM_005582.3	c.1942T>C	p.Phe648Leu	missense_variant	Exon 3 of 3	ENST00000256447.5	NP_005573.2
CD180	XM_005248504.5	c.1903T>C	p.Phe635Leu	missense_variant	Exon 4 of 4		XP_005248561.1
CD180	XM_047417178.1	c.1903T>C	p.Phe635Leu	missense_variant	Exon 4 of 4		XP_047273134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD180	ENST00000256447.5	c.1942T>C	p.Phe648Leu	missense_variant	Exon 3 of 3	1	NM_005582.3	ENSP00000256447.4

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8195 AN: 152150 Hom.: 454 Cov.: 32

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0454

GnomAD2 exomes AF: 0.0738 AC: 18442 AN: 249928 AF XY: 0.0662

Gnomad AFR exome AF: 0.0689

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.0230

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.0389

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0581

GnomAD4 exome AF: 0.0319 AC: 46518 AN: 1460354 Hom.: 2951 Cov.: 32 AF XY: 0.0322 AC XY: 23377 AN XY: 726394

African (AFR) AF: 0.0696 AC: 2322 AN: 33362

American (AMR) AF: 0.226 AC: 10053 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 616 AN: 26078

East Asian (EAS) AF: 0.208 AC: 8268 AN: 39686

South Asian (SAS) AF: 0.0855 AC: 7347 AN: 85930

European-Finnish (FIN) AF: 0.0372 AC: 1987 AN: 53416

Middle Eastern (MID) AF: 0.0211 AC: 121 AN: 5746

European-Non Finnish (NFE) AF: 0.0119 AC: 13192 AN: 1111360

Other (OTH) AF: 0.0433 AC: 2612 AN: 60330

GnomAD4 genome AF: 0.0541 AC: 8239 AN: 152268 Hom.: 464 Cov.: 32 AF XY: 0.0579 AC XY: 4313 AN XY: 74454

African (AFR) AF: 0.0720 AC: 2989 AN: 41526

American (AMR) AF: 0.143 AC: 2194 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1064 AN: 5178

South Asian (SAS) AF: 0.0970 AC: 468 AN: 4824

European-Finnish (FIN) AF: 0.0379 AC: 402 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0128 AC: 874 AN: 68026

Other (OTH) AF: 0.0487 AC: 103 AN: 2116

Alfa AF: 0.0325 Hom.: 944

Bravo AF: 0.0652

TwinsUK AF: 0.0129 AC: 48

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.0667 AC: 294

ESP6500EA AF: 0.0137 AC: 118

ExAC AF: 0.0668 AC: 8109

Asia WGS AF: 0.154 AC: 534 AN: 3478

EpiCase AF: 0.0122

EpiControl AF: 0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.2
DANN	Benign	0.48
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.095
Sift	Benign	0.22	T
Sift4G	Benign	0.62	T
Polyphen		0.0010	B
Vest4		0.075
MutPred		0.16		Loss of ubiquitination at K651 (P = 0.0755);
MPC		0.065
ClinPred		0.0054	T
GERP RS		2.9
Varity_R		0.038
gMVP		0.75
Mutation Taster		=95/5	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: rs2230524; hg19: chr5-66478729; COSMIC: COSV56517292; COSMIC: COSV56517292;