rs186309136

Variant names:

• chr12-7485410-A-C
• rs186309136
• NM_203416.4:c.2465T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-7485410-A-C
• chr12-7485410-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203416.4(CD163):​c.2465T>G​(p.Met822Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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: not found (cov: 32)
• Consequence: CD163 NM_203416.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

Genes affected

CD163 (HGNC:1631): (CD163 molecule) The protein encoded by this gene is a member of the scavenger receptor cysteine-rich (SRCR) superfamily, and is exclusively expressed in monocytes and macrophages. It functions as an acute phase-regulated receptor involved in the clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages, and may thereby protect tissues from free hemoglobin-mediated oxidative damage. This protein may also function as an innate immune sensor for bacteria and inducer of local inflammation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD163	NM_203416.4	c.2465T>G	p.Met822Arg	missense_variant	Exon 11 of 17	ENST00000432237.3	NP_981961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD163	ENST00000432237.3	c.2465T>G	p.Met822Arg	missense_variant	Exon 11 of 17	1	NM_203416.4	ENSP00000403885.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0019	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T;.;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.33	T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N;.;.;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.94	P;.;D;B
Vest4		0.63
MutPred		0.61		Gain of sheet (P = 0.039);.;.;Gain of sheet (P = 0.039);
MVP		0.45
MPC		1.1
ClinPred		0.49	T
GERP RS		4.3
Varity_R		0.86
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs186309136; hg19: chr12-7638006;