17-7580783-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001251.3(CD68):c.760C>G(p.Gln254Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 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: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CD68
NM_001251.3 missense, splice_region

Scores

Splicing: ADA: 0.00006218

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053912252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD68	NM_001251.3	MANE Select	c.760C>G	p.Gln254Glu	missense splice_region	Exon 4 of 6	NP_001242.2
	CD68	NM_001040059.2		c.679C>G	p.Gln227Glu	missense splice_region	Exon 4 of 6	NP_001035148.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD68	ENST00000250092.11	TSL:1 MANE Select	c.760C>G	p.Gln254Glu	missense splice_region	Exon 4 of 6	ENSP00000250092.6
CD68	ENST00000380498.10	TSL:1	c.679C>G	p.Gln227Glu	missense splice_region	Exon 4 of 6	ENSP00000369867.6
CD68	ENST00000584180.1	TSL:2	c.163C>G	p.Gln55Glu	missense splice_region	Exon 2 of 3	ENSP00000462198.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251448

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111944

Other (OTH)

AF:

0.0000331

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.0

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.096

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.59

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.10

PhyloP100

0.85

PrimateAI

Benign

0.31

PROVEAN

Benign

0.41

REVEL

Benign

0.019

Sift

Benign

0.77

Sift4G

Uncertain

0.013

Polyphen

0.012

Vest4

0.099

MutPred

0.46

Loss of sheet (P = 0.0817)

MVP

0.18

MPC

0.12

ClinPred

0.018

GERP RS

2.0

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.10

gMVP

0.18

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000062

dbscSNV1_RF

Benign

0.17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over