5-67185241-G-T

Position:

• chr5-67185241-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005582.3(CD180):​c.257+610C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 141,720 control chromosomes in the GnomAD database, including 3,591 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 0.20 (3591 hom., cov: 27)
• Consequence: CD180 NM_005582.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD180	NM_005582.3	c.257+610C>A		intron_variant		ENST00000256447.5	NP_005573.2
CD180	XM_005248504.5	c.218+610C>A		intron_variant			XP_005248561.1
CD180	XM_047417178.1	c.218+610C>A		intron_variant			XP_047273134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD180	ENST00000256447.5	c.257+610C>A		intron_variant		1	NM_005582.3	ENSP00000256447	P1
CD180	ENST00000515027.1	n.447+610C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 28967 AN: 141656 Hom.: 3587 Cov.: 27

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.270

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 28967 AN: 141720 Hom.: 3591 Cov.: 27 AF XY: 0.201 AC XY: 13757 AN XY: 68600

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.207

Alfa AF: 0.256 Hom.: 5699

Bravo AF: 0.182

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1697143; hg19: chr5-66481069;