chr12-7485152-G-A

Variant names:

• chr12-7485152-G-A
• rs1490894669
• NM_203416.4:c.2723C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203416.4(CD163):​c.2723C>T​(p.Ser908Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CD163 NM_203416.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2690763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD163	NM_203416.4	c.2723C>T	p.Ser908Phe	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.2723C>T	p.Ser908Phe	missense_variant	Exon 11 of 17	1	NM_203416.4	ENSP00000403885.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250756 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135464

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.79	T;T;D;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.1	M;.;.;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.049	D;D;D;D
Polyphen		0.95	P;.;D;D
Vest4		0.33
MutPred		0.46		Loss of disorder (P = 0.0017);.;.;Loss of disorder (P = 0.0017);
MVP		0.60
MPC		1.3
ClinPred		0.93	D
GERP RS		2.5
Varity_R		0.28
gMVP		0.73

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

Other links and lift over

dbSNP: rs1490894669; hg19: chr12-7637748; COSMIC: COSV63137144; COSMIC: COSV63137144;