rs9901673

Positions:

• chr17-7580783-C-A
• chr17-7580783-C-G
• chr17-7580783-C-T

Variant summary

Our verdict is Benign. Variant got -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. 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD68	NM_001251.3	c.760C>A	p.Gln254Lys	missense_variant, splice_region_variant	4/6	ENST00000250092.11	NP_001242.2
CD68	NM_001040059.2	c.679C>A	p.Gln227Lys	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>A	p.Gln254Lys	missense_variant, splice_region_variant	4/6	1	NM_001251.3	ENSP00000250092	P1
CD68	ENST00000380498.10	c.679C>A	p.Gln227Lys	missense_variant, splice_region_variant	4/6	1		ENSP00000369867
CD68	ENST00000584180.1	c.166C>A	p.Gln56Lys	missense_variant, splice_region_variant	2/3	2		ENSP00000462198

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

GnomAD3 exomes AF: 0.148 AC: 37310 AN: 251448 Hom.: 2952 AF XY: 0.149 AC XY: 20250 AN XY: 135894

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 SAS exome AF: 0.148

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

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.0981

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.0953

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.167

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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.148

Alfa AF: 0.157 Hom.: 4974

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 v4.3

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;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N;.
MutationTaster	Benign	0.88	P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.58	N;.
REVEL	Benign	0.040
Sift	Benign	0.053	T;.
Sift4G	Uncertain	0.054	T;T
Polyphen		0.012	B;.
Vest4		0.16
MPC		0.37
ClinPred		0.0038	T
GERP RS		2.0
Varity_R		0.19
gMVP		0.23

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

Publications

LitVar

Other links and lift over

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