chr12-7488939-G-A

Variant names:

• chr12-7488939-G-A
• rs7294582
• NM_203416.4:c.1421-852C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203416.4(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 NM_203416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 1 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 -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.

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.1421-852C>T		intron	N/A	NP_981961.2	Q86VB7-3
	CD163	NM_004244.6		c.1421-852C>T		intron	N/A	NP_004235.4
	CD163	NM_001370146.1		c.1421-852C>T		intron	N/A	NP_001357075.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD163	ENST00000432237.3	TSL:1 MANE Select	c.1421-852C>T		intron	N/A	ENSP00000403885.2	Q86VB7-3
	CD163	ENST00000359156.8	TSL:1	c.1421-852C>T		intron	N/A	ENSP00000352071.4	Q86VB7-1
	CD163	ENST00000396620.7	TSL:2	c.1421-852C>T		intron	N/A	ENSP00000379863.3	C9JHR8

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

African (AFR) AF: 0.0150 AC: 623 AN: 41514

American (AMR) AF: 0.0413 AC: 632 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 89 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5194

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4828

European-Finnish (FIN) AF: 0.0774 AC: 818 AN: 10562

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0907 AC: 6164 AN: 67996

Other (OTH) AF: 0.0531 AC: 112 AN: 2110

Alfa AF: 0.0628 Hom.: 312

Bravo AF: 0.0518

Asia WGS AF: 0.00838 AC: 29 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.75
DANN	Benign	0.73
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs7294582;

hg19: chr12-7641535;

COSMIC: COSV63133940;

COSMIC: COSV63133940;