rs9901673

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001251.3(CD68):c.760C>A(p.Gln254Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,568 control chromosomes in the GnomAD database, including 22,331 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 1953 hom., cov: 31)

Exomes 𝑓: 0.16 ( 20378 hom. )

Consequence

CD68
NM_001251.3 missense, splice_region

Scores

Splicing: ADA: 0.00008383

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.846

Publications

46 publications found

Variant links:

Genes affected

CD68 (HGNC:1693): (CD68 molecule) This gene encodes a 110-kD transmembrane glycoprotein that is highly expressed by human monocytes and tissue macrophages. It is a member of the lysosomal/endosomal-associated membrane glycoprotein (LAMP) family. The protein primarily localizes to lysosomes and endosomes with a smaller fraction circulating to the cell surface. It is a type I integral membrane protein with a heavily glycosylated extracellular domain and binds to tissue- and organ-specific lectins or selectins. The protein is also a member of the scavenger receptor family. Scavenger receptors typically function to clear cellular debris, promote phagocytosis, and mediate the recruitment and activation of macrophages. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

CD68 links:

ENSG00000264772 (HGNC:):

ENSG00000264772 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016418695).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD68	NM_001251.3 link	c.760C>A	p.Gln254Lys	missense_variant, splice_region_variant	Exon 4 of 6	ENST00000250092.11	NP_001242.2
CD68	NM_001040059.2 link	c.679C>A	p.Gln227Lys	missense_variant, splice_region_variant	Exon 4 of 6		NP_001035148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CD68	ENST00000250092.11 link	c.760C>A	p.Gln254Lys	missense_variant, splice_region_variant	Exon 4 of 6	1	NM_001251.3	ENSP00000250092.6
CD68	ENST00000380498.10 link	c.679C>A	p.Gln227Lys	missense_variant, splice_region_variant	Exon 4 of 6	1		ENSP00000369867.6
CD68	ENST00000584180.1 link	c.163C>A	p.Gln55Lys	missense_variant, splice_region_variant	Exon 2 of 3	2		ENSP00000462198.1
ENSG00000264772	ENST00000581621.1 link	n.3736C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 10 of 12	2

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23935

AN:

151820

Hom.:

1946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.0819

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.148

AC:

37310

AN:

251448

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.0957

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0906

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.165

AC:

240535

AN:

1461628

Hom.:

20378

Cov.:

AF XY:

0.163

AC XY:

118576

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.183

AC:

6112

AN:

33478

American (AMR)

AF:

0.0981

AC:

4388

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4732

AN:

26134

East Asian (EAS)

AF:

0.168

AC:

6682

AN:

39700

South Asian (SAS)

AF:

0.147

AC:

12713

AN:

86254

European-Finnish (FIN)

AF:

0.0953

AC:

5091

AN:

53418

Middle Eastern (MID)

AF:

0.118

AC:

683

AN:

5768

European-Non Finnish (NFE)

AF:

0.171

AC:

190076

AN:

1111778

Other (OTH)

AF:

0.167

AC:

10058

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

11091

22181

33272

44362

55453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6878

13756

20634

27512

34390

<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:

0.158

AC:

23952

AN:

151940

Hom.:

1953

Cov.:

AF XY:

0.153

AC XY:

11368

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.179

AC:

7416

AN:

41378

American (AMR)

AF:

0.125

AC:

1910

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

627

AN:

3472

East Asian (EAS)

AF:

0.158

AC:

816

AN:

5154

South Asian (SAS)

AF:

0.160

AC:

770

AN:

4820

European-Finnish (FIN)

AF:

0.0819

AC:

868

AN:

10596

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11072

AN:

67930

Other (OTH)

AF:

0.148

AC:

311

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1003

2006

3008

4011

5014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.159

Hom.:

8046

Bravo

AF:

0.165

TwinsUK

AF:

0.173

AC:

641

ALSPAC

AF:

0.170

AC:

654

ESP6500AA

AF:

0.179

AC:

787

ESP6500EA

AF:

0.168

AC:

1443

ExAC

AF:

0.154

AC:

18754

Asia WGS

AF:

0.177

AC:

615

AN:

3478

EpiCase

AF:

0.159

EpiControl

AF:

0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.72

N;.

PhyloP100

0.85

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.58

N;.

REVEL

Benign

0.040

Sift

Benign

0.053

T;.

Sift4G

Uncertain

0.054

T;T

Vest4

0.16

ClinPred

0.0038

GERP RS

2.0

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.19

gMVP

0.23

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000084

dbscSNV1_RF

Benign

0.032

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