dbSNP rs9901675: CD68:p.Ala350Thr (chr17-7581494-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_001251.3(CD68):c.1048G>A(p.Ala350Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,614,022 control chromosomes in the GnomAD database, including 2,547 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.055 ( 254 hom., cov: 31)

Exomes 𝑓: 0.053 ( 2293 hom. )

Consequence

CD68
NM_001251.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.657

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=0.0021208525).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD68	NM_001251.3 link	c.1048G>A	p.Ala350Thr	missense_variant	Exon 6 of 6	ENST00000250092.11	NP_001242.2	P34810-1
CD68	NM_001040059.2 link	c.967G>A	p.Ala323Thr	missense_variant	Exon 6 of 6		NP_001035148.1	P34810-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD68	ENST00000250092.11 link	c.1048G>A	p.Ala350Thr	missense_variant	Exon 6 of 6	1	NM_001251.3	ENSP00000250092.6	P34810-1
CD68	ENST00000380498.10 link	c.967G>A	p.Ala323Thr	missense_variant	Exon 6 of 6	1		ENSP00000369867.6	P34810-3
ENSG00000264772	ENST00000581621.1 link	n.4024G>A		non_coding_transcript_exon_variant	Exon 12 of 12	2
CD68	ENST00000584180.1 link	c.*399G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000462198.1	J3KRX0

Frequencies

GnomAD3 genomes

AF:

0.0551

AC:

8378

AN:

152118

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0712

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.0418

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0262

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0491

Gnomad OTH

AF:

0.0517

GnomAD2 exomes

AF:

0.0542

AC:

13627

AN:

251372

AF XY:

0.0565

show subpopulations

Gnomad AFR exome

AF:

0.0693

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.0584

Gnomad EAS exome

AF:

0.0426

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.0514

Gnomad OTH exome

AF:

0.0533

GnomAD4 exome

AF:

0.0531

AC:

77647

AN:

1461786

Hom.:

2293

Cov.:

AF XY:

0.0547

AC XY:

39809

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0739

AC:

2474

AN:

33468

American (AMR)

AF:

0.0346

AC:

1546

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0572

AC:

1494

AN:

26136

East Asian (EAS)

AF:

0.0521

AC:

2067

AN:

39698

South Asian (SAS)

AF:

0.104

AC:

8991

AN:

86256

European-Finnish (FIN)

AF:

0.0293

AC:

1562

AN:

53398

Middle Eastern (MID)

AF:

0.0596

AC:

344

AN:

5768

European-Non Finnish (NFE)

AF:

0.0501

AC:

55718

AN:

1111952

Other (OTH)

AF:

0.0571

AC:

3451

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3817

7633

11450

15266

19083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2178

4356

6534

8712

10890

<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:

0.0551

AC:

8392

AN:

152236

Hom.:

254

Cov.:

AF XY:

0.0549

AC XY:

4084

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0712

AC:

2958

AN:

41518

American (AMR)

AF:

0.0454

AC:

694

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

208

AN:

3472

East Asian (EAS)

AF:

0.0419

AC:

217

AN:

5178

South Asian (SAS)

AF:

0.107

AC:

515

AN:

4828

European-Finnish (FIN)

AF:

0.0262

AC:

278

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0491

AC:

3341

AN:

68014

Other (OTH)

AF:

0.0545

AC:

115

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

399

797

1196

1594

1993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0524

Hom.:

873

Bravo

AF:

0.0550

TwinsUK

AF:

0.0529

AC:

196

ALSPAC

AF:

0.0462

AC:

178

ESP6500AA

AF:

0.0679

AC:

299

ESP6500EA

AF:

0.0483

AC:

415

ExAC

AF:

0.0578

AC:

7013

Asia WGS

AF:

0.101

AC:

353

AN:

3478

EpiCase

AF:

0.0449

EpiControl

AF:

0.0485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.058

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.48

N;.

PhyloP100

-0.66

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.015

Sift

Benign

0.76

T;.

Sift4G

Benign

0.57

T;T

Polyphen

0.0010

B;.

Vest4

0.0050

MPC

0.095

ClinPred

0.00030

GERP RS

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.49

Mutation Taster

=98/2

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