12-7485410-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_203416.4(CD163):​c.2465T>C​(p.Met822Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,610,436 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (2 hom.)
• Consequence: CD163 NM_203416.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.874
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050034195).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203416.4. 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
	CD163	NM_203416.4	MANE Select	c.2465T>C	p.Met822Thr	missense	Exon 11 of 17	NP_981961.2	Q86VB7-3
	CD163	NM_004244.6		c.2465T>C	p.Met822Thr	missense	Exon 11 of 17	NP_004235.4
	CD163	NM_001370146.1		c.2465T>C	p.Met822Thr	missense	Exon 11 of 16	NP_001357075.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD163	ENST00000432237.3	TSL:1 MANE Select	c.2465T>C	p.Met822Thr	missense	Exon 11 of 17	ENSP00000403885.2	Q86VB7-3
	CD163	ENST00000359156.8	TSL:1	c.2465T>C	p.Met822Thr	missense	Exon 11 of 17	ENSP00000352071.4	Q86VB7-1
	CD163	ENST00000396620.7	TSL:2	c.2564T>C	p.Met855Thr	missense	Exon 10 of 16	ENSP00000379863.3	C9JHR8

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000766 AC: 19 AN: 248138 AF XY: 0.000104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000398 AC: 58 AN: 1458112 Hom.: 2 Cov.: 32 AF XY: 0.0000483 AC XY: 35 AN XY: 724748

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.000293 AC: 13 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39612

South Asian (SAS) AF: 0.000372 AC: 32 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5744

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1109344

Other (OTH) AF: 0.0000830 AC: 5 AN: 60242

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41590

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.44
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.96	N
PhyloP100		0.87
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.14	T
Sift4G	Benign	0.68	T
Polyphen		0.038	B
Vest4		0.33
MVP		0.26
MPC		0.51
ClinPred		0.030	T
GERP RS		4.3
Varity_R		0.17
gMVP		0.45
Mutation Taster		=81/19	polymorphism

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: rs186309136; hg19: chr12-7638006;