rs9901675

Positions:

• chr17-7581494-G-A

Variant summary

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

The NM_001251.3(CD68):​c.1048G>A​(p.Ala350Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,614,022 control chromosomes in the GnomAD database, including 2,547 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.055 (254 hom., cov: 31)
  • Exomes 𝑓: 0.053 (2293 hom.)
• Consequence: CD68 NM_001251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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 (MetaRNN=0.0021208525).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD68	NM_001251.3	c.1048G>A	p.Ala350Thr	missense_variant	6/6	ENST00000250092.11	NP_001242.2
CD68	NM_001040059.2	c.967G>A	p.Ala323Thr	missense_variant	6/6		NP_001035148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD68	ENST00000250092.11	c.1048G>A	p.Ala350Thr	missense_variant	6/6	1	NM_001251.3	ENSP00000250092.6
CD68	ENST00000380498.10	c.967G>A	p.Ala323Thr	missense_variant	6/6	1		ENSP00000369867.6
CD68	ENST00000584180.1	c.*399G>A		3_prime_UTR_variant	3/3	2		ENSP00000462198.1
ENSG00000264772	ENST00000581621.1	n.4024G>A		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8378 AN: 152118 Hom.: 251 Cov.: 31

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0517

GnomAD3 exomes AF: 0.0542 AC: 13627 AN: 251372 Hom.: 443 AF XY: 0.0565 AC XY: 7676 AN XY: 135858

Gnomad AFR exome AF: 0.0693

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.0584

Gnomad EAS exome AF: 0.0426

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.0287

Gnomad NFE exome AF: 0.0514

Gnomad OTH exome AF: 0.0533

GnomAD4 exome AF: 0.0531 AC: 77647 AN: 1461786 Hom.: 2293 Cov.: 33 AF XY: 0.0547 AC XY: 39809 AN XY: 727194

Gnomad4 AFR exome AF: 0.0739

Gnomad4 AMR exome AF: 0.0346

Gnomad4 ASJ exome AF: 0.0572

Gnomad4 EAS exome AF: 0.0521

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0293

Gnomad4 NFE exome AF: 0.0501

Gnomad4 OTH exome AF: 0.0571

GnomAD4 genome AF: 0.0551 AC: 8392 AN: 152236 Hom.: 254 Cov.: 31 AF XY: 0.0549 AC XY: 4084 AN XY: 74440

Gnomad4 AFR AF: 0.0712

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.0419

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0262

Gnomad4 NFE AF: 0.0491

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0509 Hom.: 429

Bravo AF: 0.0550

TwinsUK AF: 0.0529 AC: 196

ALSPAC AF: 0.0462 AC: 178

ESP6500AA AF: 0.0679 AC: 299

ESP6500EA AF: 0.0483 AC: 415

ExAC AF: 0.0578 AC: 7013

Asia WGS AF: 0.101 AC: 353 AN: 3478

EpiCase AF: 0.0449

EpiControl AF: 0.0485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.058
DANN	Benign	0.74
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.48	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.015
Sift	Benign	0.76	T;.
Sift4G	Benign	0.57	T;T
Polyphen		0.0010	B;.
Vest4		0.0050
MPC		0.095
ClinPred		0.00030	T
GERP RS		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.49

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: rs9901675; hg19: chr17-7484812; COSMIC: COSV51510059; COSMIC: COSV51510059;