rs9896688

Positions:

• chr17-7580597-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001251.3(CD68):​c.687+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,362 control chromosomes in the GnomAD database, including 15,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1629 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13590 hom.)
• Consequence: CD68 NM_001251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD68	NM_001251.3	c.687+12A>T		intron_variant		ENST00000250092.11	NP_001242.2
CD68	NM_001040059.2	c.606+12A>T		intron_variant			NP_001035148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD68	ENST00000250092.11	c.687+12A>T		intron_variant		1	NM_001251.3	ENSP00000250092.6
CD68	ENST00000380498.10	c.606+12A>T		intron_variant		1		ENSP00000369867.6
CD68	ENST00000584180.1	c.90+12A>T		intron_variant		2		ENSP00000462198.1
ENSG00000264772	ENST00000581621.1	n.3663+12A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21301 AN: 151550 Hom.: 1622 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.132 AC: 33280 AN: 251332 Hom.: 2499 AF XY: 0.135 AC XY: 18344 AN XY: 135830

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.0541

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.134 AC: 195529 AN: 1461694 Hom.: 13590 Cov.: 35 AF XY: 0.135 AC XY: 98071 AN XY: 727138

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.0562

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.141 AC: 21326 AN: 151668 Hom.: 1629 Cov.: 31 AF XY: 0.141 AC XY: 10468 AN XY: 74124

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0935

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.135

Alfa AF: 0.141 Hom.: 279

Bravo AF: 0.134

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs9896688; hg19: chr17-7483915; COSMIC: COSV51509726; COSMIC: COSV51509726;