Variant 12-7485199-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_203416.4(CD163):c.2676T>C(p.Asn892=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,614,154 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 225 hom. )

Consequence

CD163
NM_203416.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.919

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 12-7485199-A-G is Benign according to our data. Variant chr12-7485199-A-G is described in ClinVar as [Benign]. Clinvar id is 779946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.919 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD163	NM_203416.4 linkuse as main transcript	c.2676T>C	p.Asn892=	synonymous_variant	11/17	ENST00000432237.3	NP_981961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD163	ENST00000432237.3 linkuse as main transcript	c.2676T>C	p.Asn892=	synonymous_variant	11/17	1	NM_203416.4	ENSP00000403885	P1	Q86VB7-3

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

803

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.0593

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00866

AC:

2175

AN:

251162

Hom.:

AF XY:

0.00903

AC XY:

1226

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.0521

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00329

Gnomad OTH exome

AF:

0.00881

GnomAD4 exome

AF:

0.00625

AC:

9131

AN:

1461830

Hom.:

225

Cov.:

AF XY:

0.00668

AC XY:

4855

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.0875

Gnomad4 SAS exome

AF:

0.0175

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.00258

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00528

AC:

805

AN:

152324

Hom.:

Cov.:

AF XY:

0.00589

AC XY:

439

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.0594

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00466

Hom.:

Bravo

AF:

0.00518

EpiCase

AF:

0.00409

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.0

DANN

Benign

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over