Variant rs2230524 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.054 ( 464 hom., cov: 32)

Exomes 𝑓: 0.032 ( 2951 hom. )

Consequence

CD180
NM_005582.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Variant links:

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]

CD180 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CD180	NM_005582.3 link	c.1942T>C	p.Phe648Leu	missense_variant	3/3	ENST00000256447.5	NP_005573.2	Q99467
CD180	XM_005248504.5 link	c.1903T>C	p.Phe635Leu	missense_variant	4/4		XP_005248561.1
CD180	XM_047417178.1 link	c.1903T>C	p.Phe635Leu	missense_variant	4/4		XP_047273134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD180	ENST00000256447.5 link	c.1942T>C	p.Phe648Leu	missense_variant	3/3	1	NM_005582.3	ENSP00000256447.4		Q99467

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8195

AN:

152150

Hom.:

454

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0738

AC:

18442

AN:

249928

Hom.:

1699

AF XY:

0.0662

AC XY:

8946

AN XY:

135062

show subpopulations

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 SAS exome

AF:

0.0872

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.:

AF XY:

0.0322

AC XY:

23377

AN XY:

726394

show subpopulations

Gnomad4 AFR exome

AF:

0.0696

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.0236

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.0855

Gnomad4 FIN exome

AF:

0.0372

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.0433

GnomAD4 genome

AF:

0.0541

AC:

8239

AN:

152268

Hom.:

464

Cov.:

AF XY:

0.0579

AC XY:

4313

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.0970

Gnomad4 FIN

AF:

0.0379

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0314

Hom.:

486

Bravo

AF:

0.0652

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.00934

AC:

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.2

DANN

Benign

0.48

DEOGEN2

Benign

0.023

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.85

PrimateAI

Benign

0.41

PROVEAN

Benign

0.27

REVEL

Benign

0.095

Sift

Benign

0.22

Sift4G

Benign

0.62

Polyphen

0.0010

Vest4

0.075

MutPred

0.16

Loss of ubiquitination at K651 (P = 0.0755);

MPC

0.065

ClinPred

0.0054

GERP RS

2.9

Varity_R

0.038

gMVP

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over