chr17-7581494-G-A

Variant names:

• chr17-7581494-G-A
• rs9901675
• NM_001251.3:c.1048G>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.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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A350S) has been classified as Uncertain significance.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD68	NM_001251.3	MANE Select	c.1048G>A	p.Ala350Thr	missense	Exon 6 of 6	NP_001242.2	P34810-1
	CD68	NM_001040059.2		c.967G>A	p.Ala323Thr	missense	Exon 6 of 6	NP_001035148.1	P34810-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD68	ENST00000250092.11	TSL:1 MANE Select	c.1048G>A	p.Ala350Thr	missense	Exon 6 of 6	ENSP00000250092.6	P34810-1
	CD68	ENST00000380498.10	TSL:1	c.967G>A	p.Ala323Thr	missense	Exon 6 of 6	ENSP00000369867.6	P34810-3
	CD68	ENST00000852832.1		c.949G>A	p.Ala317Thr	missense	Exon 6 of 6	ENSP00000522891.1

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

GnomAD2 exomes AF: 0.0542 AC: 13627 AN: 251372 AF XY: 0.0565

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 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

African (AFR) AF: 0.0739 AC: 2474 AN: 33468

American (AMR) AF: 0.0346 AC: 1546 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0572 AC: 1494 AN: 26136

East Asian (EAS) AF: 0.0521 AC: 2067 AN: 39698

South Asian (SAS) AF: 0.104 AC: 8991 AN: 86256

European-Finnish (FIN) AF: 0.0293 AC: 1562 AN: 53398

Middle Eastern (MID) AF: 0.0596 AC: 344 AN: 5768

European-Non Finnish (NFE) AF: 0.0501 AC: 55718 AN: 1111952

Other (OTH) AF: 0.0571 AC: 3451 AN: 60386

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

African (AFR) AF: 0.0712 AC: 2958 AN: 41518

American (AMR) AF: 0.0454 AC: 694 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5178

South Asian (SAS) AF: 0.107 AC: 515 AN: 4828

European-Finnish (FIN) AF: 0.0262 AC: 278 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0491 AC: 3341 AN: 68014

Other (OTH) AF: 0.0545 AC: 115 AN: 2112

Alfa AF: 0.0524 Hom.: 873

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 v4.9

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
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.48	N
PhyloP100		-0.66
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.015
Sift	Benign	0.76	T
Sift4G	Benign	0.57	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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