chr17-7580783-C-A

Variant names:

• chr17-7580783-C-A
• rs9901673
• NM_001251.3:c.760C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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

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.

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>A	p.Gln254Lys	missense splice_region	Exon 4 of 6	NP_001242.2
	CD68	NM_001040059.2		c.679C>A	p.Gln227Lys	missense splice_region	Exon 4 of 6	NP_001035148.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD68	ENST00000250092.11	TSL:1 MANE Select	c.760C>A	p.Gln254Lys	missense splice_region	Exon 4 of 6	ENSP00000250092.6
	CD68	ENST00000380498.10	TSL:1	c.679C>A	p.Gln227Lys	missense splice_region	Exon 4 of 6	ENSP00000369867.6
	CD68	ENST00000584180.1	TSL:2	c.163C>A	p.Gln55Lys	missense splice_region	Exon 2 of 3	ENSP00000462198.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23935 AN: 151820 Hom.: 1946 Cov.: 31

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

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.: 34 AF XY: 0.163 AC XY: 118576 AN XY: 727130

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

GnomAD4 genome AF: 0.158 AC: 23952 AN: 151940 Hom.: 1953 Cov.: 31 AF XY: 0.153 AC XY: 11368 AN XY: 74284

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: 19 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11072 AN: 67930

Other (OTH) AF: 0.148 AC: 311 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.72
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N
PhyloP100		0.85
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.040
Sift	Benign	0.053	T
Sift4G	Uncertain	0.054	T
Polyphen		0.012	B
Vest4		0.16
MPC		0.37
ClinPred		0.0038	T
GERP RS		2.0
PromoterAI		-0.037	Neutral
Varity_R		0.19
gMVP		0.23
Mutation Taster		=89/11	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9901673; hg19: chr17-7484101; COSMIC: COSV51510985; COSMIC: COSV51510985;