chr12-7496888-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_203416.4(CD163):c.1024A>G(p.Ile342Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 1,613,920 control chromosomes in the GnomAD database, including 711,910 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 56630 hom., cov: 32)

Exomes 𝑓: 0.94 ( 655280 hom. )

Consequence

CD163
NM_203416.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.07

Publications

36 publications found

Variant links:

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]

CD163 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6509773E-6).

BP6

Variant 12-7496888-T-C is Benign according to our data. Variant chr12-7496888-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD163	NM_203416.4	MANE Select	c.1024A>G	p.Ile342Val	missense	Exon 5 of 17	NP_981961.2
CD163	NM_004244.6		c.1024A>G	p.Ile342Val	missense	Exon 5 of 17	NP_004235.4
CD163	NM_001370146.1		c.1024A>G	p.Ile342Val	missense	Exon 5 of 16	NP_001357075.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD163	ENST00000432237.3	TSL:1 MANE Select	c.1024A>G	p.Ile342Val	missense	Exon 5 of 17	ENSP00000403885.2
CD163	ENST00000359156.8	TSL:1	c.1024A>G	p.Ile342Val	missense	Exon 5 of 17	ENSP00000352071.4
CD163	ENST00000396620.7	TSL:2	c.1024A>G	p.Ile342Val	missense	Exon 5 of 16	ENSP00000379863.3

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128998

AN:

152058

Hom.:

56597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.984

Gnomad AMR

AF:

0.853

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

0.706

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.972

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.969

Gnomad OTH

AF:

0.869

GnomAD2 exomes

AF:

0.889

AC:

223003

AN:

250984

AF XY:

0.898

show subpopulations

Gnomad AFR exome

AF:

0.604

Gnomad AMR exome

AF:

0.805

Gnomad ASJ exome

AF:

0.973

Gnomad EAS exome

AF:

0.691

Gnomad FIN exome

AF:

0.974

Gnomad NFE exome

AF:

0.969

Gnomad OTH exome

AF:

0.924

GnomAD4 exome

AF:

0.943

AC:

1379100

AN:

1461744

Hom.:

655280

Cov.:

AF XY:

0.943

AC XY:

685551

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.602

AC:

20147

AN:

33468

American (AMR)

AF:

0.810

AC:

36219

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.974

AC:

25465

AN:

26136

East Asian (EAS)

AF:

0.721

AC:

28609

AN:

39686

South Asian (SAS)

AF:

0.860

AC:

74186

AN:

86254

European-Finnish (FIN)

AF:

0.972

AC:

51915

AN:

53408

Middle Eastern (MID)

AF:

0.930

AC:

5360

AN:

5766

European-Non Finnish (NFE)

AF:

0.973

AC:

1081401

AN:

1111912

Other (OTH)

AF:

0.924

AC:

55798

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

3981

7963

11944

15926

19907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21552

43104

64656

86208

107760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.848

AC:

129096

AN:

152176

Hom.:

56630

Cov.:

AF XY:

0.848

AC XY:

63079

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.619

AC:

25636

AN:

41448

American (AMR)

AF:

0.853

AC:

13048

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.973

AC:

3377

AN:

3472

East Asian (EAS)

AF:

0.706

AC:

3648

AN:

5164

South Asian (SAS)

AF:

0.850

AC:

4098

AN:

4820

European-Finnish (FIN)

AF:

0.972

AC:

10327

AN:

10624

Middle Eastern (MID)

AF:

0.925

AC:

272

AN:

294

European-Non Finnish (NFE)

AF:

0.969

AC:

65953

AN:

68038

Other (OTH)

AF:

0.870

AC:

1840

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

825

1650

2475

3300

4125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.926

Hom.:

308461

Bravo

AF:

0.827

TwinsUK

AF:

0.970

AC:

3598

ALSPAC

AF:

0.975

AC:

3756

ESP6500AA

AF:

0.626

AC:

2759

ESP6500EA

AF:

0.968

AC:

8324

ExAC

AF:

0.887

AC:

107673

Asia WGS

AF:

0.797

AC:

2773

AN:

3478

EpiCase

AF:

0.966

EpiControl

AF:

0.968

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.062

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.10

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.52

REVEL

Benign

0.026

Sift

Benign

0.20

Sift4G

Uncertain

0.033

Polyphen

0.0040

Vest4

0.065

MPC

0.37

ClinPred

0.0027

GERP RS

-1.5

Varity_R

0.033

gMVP

0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over