rs6488340

Positions:

• chr12-7483197-G-A
• chr12-7483197-G-C

Variant summary

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

The ENST00000432237.3(CD163):​c.3088+170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 772,760 control chromosomes in the GnomAD database, including 288,474 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 0.78 (48472 hom., cov: 30)
  • Exomes 𝑓: 0.87 (240002 hom.)
• Consequence: CD163 ENST00000432237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD163	NM_203416.4	c.3088+170C>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.3088+170C>T		intron_variant		1	NM_203416.4	ENSP00000403885	P1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118019 AN: 152008 Hom.: 48450 Cov.: 30

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.791

GnomAD4 exome AF: 0.874 AC: 542163 AN: 620634 Hom.: 240002 Cov.: 8 AF XY: 0.874 AC XY: 281544 AN XY: 322228

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.917

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.934

Gnomad4 NFE exome AF: 0.911

Gnomad4 OTH exome AF: 0.858

GnomAD4 genome AF: 0.776 AC: 118091 AN: 152126 Hom.: 48472 Cov.: 30 AF XY: 0.778 AC XY: 57897 AN XY: 74390

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.921

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.941

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.793

Alfa AF: 0.848 Hom.: 11508

Bravo AF: 0.751

Asia WGS AF: 0.729 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.29

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: rs6488340; hg19: chr12-7635793;