rs7294582

Positions:

• chr12-7488939-G-A
• chr12-7488939-G-C

Variant summary

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

The ENST00000432237.3(CD163):​c.1421-852C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,166 control chromosomes in the GnomAD database, including 333 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 0.056 (333 hom., cov: 32)
• Consequence: CD163 ENST00000432237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD163	NM_203416.4	c.1421-852C>T		intron_variant		ENST00000432237.3	NP_981961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD163	ENST00000432237.3	c.1421-852C>T		intron_variant		1	NM_203416.4	ENSP00000403885	P1

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8564 AN: 152048 Hom.: 333 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0563 AC: 8566 AN: 152166 Hom.: 333 Cov.: 32 AF XY: 0.0526 AC XY: 3916 AN XY: 74396

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0257

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0638 Hom.: 117

Bravo AF: 0.0518

Asia WGS AF: 0.00838 AC: 29 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.75
DANN	Benign	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: rs7294582; hg19: chr12-7641535; COSMIC: COSV63133940; COSMIC: COSV63133940;