chr17-7580783-C-G

Position:

• chr17-7580783-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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

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]

ENSG00000264772 (HGNC:):

ACMG classification

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	c.760C>G	p.Gln254Glu	missense_variant, splice_region_variant	4/6	ENST00000250092.11	NP_001242.2
CD68	NM_001040059.2	c.679C>G	p.Gln227Glu	missense_variant, splice_region_variant	4/6		NP_001035148.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251448 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135894

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: 4 AN: 1461822 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

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.: 31

ExAC AF: 0.00000824 AC: 1

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	T
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	N
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.10	N;.
PrimateAI	Benign	0.31	T
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	T
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

Other links and lift over

dbSNP: rs9901673; hg19: chr17-7484101;