Genetic Variant CD163:c.3088+170C>T (chr12-7483197-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203416.4(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
NM_203416.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.282

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD163	NM_203416.4 link	c.3088+170C>T		intron_variant	Intron 12 of 16	ENST00000432237.3	NP_981961.2	Q86VB7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD163	ENST00000432237.3 link	c.3088+170C>T		intron_variant	Intron 12 of 16	1	NM_203416.4	ENSP00000403885.2		Q86VB7-3

Frequencies

GnomAD3 genomes

AF:

0.776

AC:

118019

AN:

152008

Hom.:

48450

Cov.:

show subpopulations

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.:

AF XY:

0.874

AC XY:

281544

AN XY:

322228

show subpopulations

African (AFR)

AF:

0.487

AC:

7689

AN:

15796

American (AMR)

AF:

0.791

AC:

15869

AN:

20062

Ashkenazi Jewish (ASJ)

AF:

0.917

AC:

13692

AN:

14926

East Asian (EAS)

AF:

0.625

AC:

20438

AN:

32724

South Asian (SAS)

AF:

0.831

AC:

41889

AN:

50414

European-Finnish (FIN)

AF:

0.934

AC:

32033

AN:

34304

Middle Eastern (MID)

AF:

0.880

AC:

2252

AN:

2558

European-Non Finnish (NFE)

AF:

0.911

AC:

381037

AN:

418084

Other (OTH)

AF:

0.858

AC:

27264

AN:

31766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3439

6878

10318

13757

17196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4418

8836

13254

17672

22090

<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:

0.776

AC:

118091

AN:

152126

Hom.:

48472

Cov.:

AF XY:

0.778

AC XY:

57897

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.498

AC:

20653

AN:

41448

American (AMR)

AF:

0.800

AC:

12233

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.921

AC:

3198

AN:

3472

East Asian (EAS)

AF:

0.615

AC:

3174

AN:

5158

South Asian (SAS)

AF:

0.820

AC:

3948

AN:

4812

European-Finnish (FIN)

AF:

0.941

AC:

9990

AN:

10618

Middle Eastern (MID)

AF:

0.873

AC:

255

AN:

292

European-Non Finnish (NFE)

AF:

0.913

AC:

62085

AN:

68014

Other (OTH)

AF:

0.793

AC:

1677

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1088

2176

3263

4351

5439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.838

Hom.:

11594

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

(source)

DANN

Benign

0.29

PhyloP100

0.28

PromoterAI

-0.020

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over