12-7485199-A-G

Variant names:

• chr12-7485199-A-G
• rs79148200
• NM_203416.4:c.2676T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_203416.4(CD163):​c.2676T>C​(p.Asn892Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,614,154 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (225 hom.)
• Consequence: CD163 NM_203416.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.919
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-7485199-A-G is Benign according to our data. Variant chr12-7485199-A-G is described in ClinVar as Benign. ClinVar VariationId is 779946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.919 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

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.2676T>C	p.Asn892Asn	synonymous	Exon 11 of 17	NP_981961.2	Q86VB7-3
	CD163	NM_004244.6		c.2676T>C	p.Asn892Asn	synonymous	Exon 11 of 17	NP_004235.4
	CD163	NM_001370146.1		c.2676T>C	p.Asn892Asn	synonymous	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.2676T>C	p.Asn892Asn	synonymous	Exon 11 of 17	ENSP00000403885.2	Q86VB7-3
	CD163	ENST00000359156.8	TSL:1	c.2676T>C	p.Asn892Asn	synonymous	Exon 11 of 17	ENSP00000352071.4	Q86VB7-1
	CD163	ENST00000396620.7	TSL:2	c.2775T>C	p.Asn925Asn	synonymous	Exon 10 of 16	ENSP00000379863.3	C9JHR8

Frequencies

GnomAD3 genomes AF: 0.00528 AC: 803 AN: 152206 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00866 AC: 2175 AN: 251162 AF XY: 0.00903

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.0165

Gnomad EAS exome AF: 0.0521

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00329

Gnomad OTH exome AF: 0.00881

GnomAD4 exome AF: 0.00625 AC: 9131 AN: 1461830 Hom.: 225 Cov.: 33 AF XY: 0.00668 AC XY: 4855 AN XY: 727226

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.00215 AC: 96 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 427 AN: 26134

East Asian (EAS) AF: 0.0875 AC: 3472 AN: 39700

South Asian (SAS) AF: 0.0175 AC: 1506 AN: 86256

European-Finnish (FIN) AF: 0.000674 AC: 36 AN: 53420

Middle Eastern (MID) AF: 0.0163 AC: 94 AN: 5766

European-Non Finnish (NFE) AF: 0.00258 AC: 2871 AN: 1111954

Other (OTH) AF: 0.0100 AC: 606 AN: 60396

GnomAD4 genome AF: 0.00528 AC: 805 AN: 152324 Hom.: 19 Cov.: 32 AF XY: 0.00589 AC XY: 439 AN XY: 74486

African (AFR) AF: 0.00125 AC: 52 AN: 41566

American (AMR) AF: 0.00392 AC: 60 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3472

East Asian (EAS) AF: 0.0594 AC: 308 AN: 5182

South Asian (SAS) AF: 0.0160 AC: 77 AN: 4824

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00315 AC: 214 AN: 68032

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00436 Hom.: 3

Bravo AF: 0.00518

EpiCase AF: 0.00409

EpiControl AF: 0.00362

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.0
DANN	Benign	0.29
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs79148200; hg19: chr12-7637795; COSMIC: COSV63134695; COSMIC: COSV63134695;