chr12-7479969-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004244.6(CD163):c.3371G>A(p.Ser1124Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,610,914 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

CD163
NM_004244.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00100

Publications

1 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:

CD163L1 (HGNC:30375): (CD163 molecule like 1) This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. The SRCR family is defined by a 100-110 amino acid SRCR domain, which may mediate protein-protein interaction and ligand binding. The encoded protein contains twelve SRCR domains, a transmembrane region and a cytoplasmic domain. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

CD163L1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CD163L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003458649).

BP6

Variant 12-7479969-C-T is Benign according to our data. Variant chr12-7479969-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 711920.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004244.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD163	NM_203416.4	MANE Select	c.3344-56G>A		intron	N/A	NP_981961.2	Q86VB7-3
CD163	NM_004244.6		c.3371G>A	p.Ser1124Asn	missense	Exon 16 of 17	NP_004235.4
CD163	NM_001370146.1		c.3275G>A	p.Ser1092Asn	missense	Exon 15 of 16	NP_001357075.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD163	ENST00000359156.8	TSL:1	c.3371G>A	p.Ser1124Asn	missense	Exon 16 of 17	ENSP00000352071.4	Q86VB7-1
CD163	ENST00000432237.3	TSL:1 MANE Select	c.3344-56G>A		intron	N/A	ENSP00000403885.2	Q86VB7-3
CD163	ENST00000537626.5	TSL:2	c.311G>A	p.Ser104Asn	missense	Exon 4 of 5	ENSP00000439226.1	H0YFM0

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

391

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000984

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000609

AC:

151

AN:

247808

AF XY:

0.000425

show subpopulations

Gnomad AFR exome

AF:

0.00816

Gnomad AMR exome

AF:

0.000444

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000253

AC:

369

AN:

1458780

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

725674

show subpopulations

African (AFR)

AF:

0.00894

AC:

298

AN:

33334

American (AMR)

AF:

0.000383

AC:

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52850

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1110874

Other (OTH)

AF:

0.000497

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00258

AC:

392

AN:

152134

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00892

AC:

370

AN:

41496

American (AMR)

AF:

0.000983

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68018

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00107

Hom.:

Bravo

AF:

0.00304

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000799

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.5

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.073

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

-0.0010

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.080

REVEL

Benign

0.019

Sift

Benign

0.33

Sift4G

Benign

0.88

Polyphen

0.0

Vest4

0.13

MVP

0.37

MPC

0.41

ClinPred

0.014

GERP RS

-1.0

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.041

gMVP

0.049

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over