Genetic Variant CD180:p.Ser584Ser (chr5-67183091-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005582.3(CD180):c.1752G>A(p.Ser584Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00667 in 1,611,248 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 54 hom. )

Consequence

CD180
NM_005582.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.682

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 5-67183091-C-T is Benign according to our data. Variant chr5-67183091-C-T is described in ClinVar as Benign. ClinVar VariationId is 709971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.682 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 54 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005582.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD180	NM_005582.3	MANE Select	c.1752G>A	p.Ser584Ser	synonymous	Exon 3 of 3	NP_005573.2	Q99467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD180	ENST00000256447.5	TSL:1 MANE Select	c.1752G>A	p.Ser584Ser	synonymous	Exon 3 of 3	ENSP00000256447.4	Q99467

Frequencies

GnomAD3 genomes

AF:

0.00466

AC:

709

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00806

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00455

AC:

1137

AN:

249906

AF XY:

0.00462

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.000991

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00260

Gnomad NFE exome

AF:

0.00791

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00688

AC:

10034

AN:

1458968

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

4916

AN XY:

725380

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33334

American (AMR)

AF:

0.00103

AC:

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.000154

AC:

AN:

26046

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39620

South Asian (SAS)

AF:

0.00307

AC:

264

AN:

85990

European-Finnish (FIN)

AF:

0.00247

AC:

132

AN:

53378

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00829

AC:

9207

AN:

1110114

Other (OTH)

AF:

0.00553

AC:

333

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

547

1093

1640

2186

2733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00466

AC:

709

AN:

152280

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41568

American (AMR)

AF:

0.00150

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00395

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00283

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00806

AC:

548

AN:

68020

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.00429

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00557

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.1

(source)

DANN

Benign

0.74

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over