17-7579882-C-T

Position:

chr17-7579882-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001251.3(CD68):c.122C>T(p.Thr41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,048 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 10 hom., cov: 31)

Exomes 𝑓: 0.00077 ( 10 hom. )

Consequence

CD68
NM_001251.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66

Variant links:

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]

CD68 links:

ENSG00000264772 (HGNC:):

ENSG00000264772 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004093915).

BP6

Variant 17-7579882-C-T is Benign according to our data. Variant chr17-7579882-C-T is described in ClinVar as [Benign]. Clinvar id is 717429.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00663 (1009/152172) while in subpopulation AFR AF= 0.0228 (946/41482). AF 95% confidence interval is 0.0216. There are 10 homozygotes in gnomad4. There are 496 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD68	NM_001251.3 link	c.122C>T	p.Thr41Met	missense_variant	2/6	ENST00000250092.11	NP_001242.2	P34810-1
CD68	NM_001040059.2 link	c.50-9C>T		intron_variant			NP_001035148.1	P34810-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD68	ENST00000250092.11 link	c.122C>T	p.Thr41Met	missense_variant	2/6	1	NM_001251.3	ENSP00000250092.6	P34810-1
CD68	ENST00000380498.10 link	c.50-9C>T		intron_variant		1		ENSP00000369867.6	P34810-3
CD68	ENST00000584502.1 link	c.83C>T	p.Thr28Met	missense_variant	2/3	2		ENSP00000462768.1	J3KT24
ENSG00000264772	ENST00000581621.1 link	n.3098C>T		non_coding_transcript_exon_variant	8/12	2

Frequencies

GnomAD3 genomes

AF:

0.00661

AC:

1005

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00194

AC:

483

AN:

249146

Hom.:

AF XY:

0.00137

AC XY:

185

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000766

AC:

1120

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

462

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0226

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00663

AC:

1009

AN:

152172

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

496

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00772

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0229

AC:

101

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00240

AC:

291

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

M;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.23

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.47

MVP

0.47

MPC

0.49

ClinPred

0.018

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.059

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over