Variant 17-7580783-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 16/22 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q254K) has been classified as Likely benign.

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

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD68	NM_001251.3 linkuse as main transcript	c.760C>G	p.Gln254Glu	missense_variant, splice_region_variant	4/6	ENST00000250092.11	NP_001242.2	P34810-1
CD68	NM_001040059.2 linkuse as main transcript	c.679C>G	p.Gln227Glu	missense_variant, splice_region_variant	4/6		NP_001035148.1	P34810-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD68	ENST00000250092.11 linkuse as main transcript	c.760C>G	p.Gln254Glu	missense_variant, splice_region_variant	4/6	1	NM_001251.3	ENSP00000250092.6	P34810-1
CD68	ENST00000380498.10 linkuse as main transcript	c.679C>G	p.Gln227Glu	missense_variant, splice_region_variant	4/6	1		ENSP00000369867.6	P34810-3
CD68	ENST00000584180.1 linkuse as main transcript	c.163C>G	p.Gln55Glu	missense_variant, splice_region_variant	2/3	2		ENSP00000462198.1	J3KRX0
ENSG00000264772	ENST00000581621.1 linkuse as main transcript	n.3736C>G		splice_region_variant, non_coding_transcript_exon_variant	10/12	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.0

DANN

Benign

0.63

DEOGEN2

Benign

0.096

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.10

N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.41

N;.

REVEL

Benign

0.019

Sift

Benign

0.77

T;.

Sift4G

Uncertain

0.013

D;D

Polyphen

0.012

B;.

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

Varity_R

0.10

gMVP

0.18

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over