12-7481248-T-A

Variant names:

• chr12-7481248-T-A
• NM_203416.4:c.3256A>T
• CD163 p.Arg1086*

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_203416.4(CD163):​c.3256A>T​(p.Arg1086*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD163 NM_203416.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3256A>T	p.Arg1086*	stop_gained	Exon 15 of 17	NP_981961.2	Q86VB7-3
	CD163	NM_004244.6		c.3256A>T	p.Arg1086*	stop_gained	Exon 15 of 17	NP_004235.4
	CD163	NM_001370145.1		c.3256A>T	p.Arg1086*	stop_gained	Exon 15 of 17	NP_001357074.1	Q86VB7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD163	ENST00000432237.3	TSL:1 MANE Select	c.3256A>T	p.Arg1086*	stop_gained	Exon 15 of 17	ENSP00000403885.2	Q86VB7-3
	CD163	ENST00000359156.8	TSL:1	c.3256A>T	p.Arg1086*	stop_gained	Exon 15 of 17	ENSP00000352071.4	Q86VB7-1
	CD163	ENST00000396620.7	TSL:2	c.3355A>T	p.Arg1119*	stop_gained	Exon 14 of 16	ENSP00000379863.3	C9JHR8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.73	D
PhyloP100		2.1
Mutation Taster		=50/150	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-7633844;