Genetic Variant CD101:p.Arg992Trp (chr1-117034009-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256106.3(CD101):c.2974C>T(p.Arg992Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,614,030 control chromosomes in the GnomAD database, including 215 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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.021 ( 119 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 96 hom. )

Consequence

CD101
NM_001256106.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0450

Variant links:

Genes affected

CD101 (HGNC:5949): (CD101 molecule) Predicted to enable hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides. Predicted to be involved in cell surface receptor signaling pathway. Predicted to act upstream of or within positive regulation of myeloid leukocyte differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CD101 links:

CD101-AS1 (HGNC:55665): (CD101 antisense RNA 1)

CD101-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002947837).

BP6

Variant 1-117034009-C-T is Benign according to our data. Variant chr1-117034009-C-T is described in ClinVar as [Benign]. Clinvar id is 780258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD101	NM_001256106.3 link	c.2974C>T	p.Arg992Trp	missense_variant	Exon 9 of 10	ENST00000682167.1	NP_001243035.1	Q93033

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD101	ENST00000682167.1 link	c.2974C>T	p.Arg992Trp	missense_variant	Exon 9 of 10		NM_001256106.3	ENSP00000508039.1		Q93033

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3172

AN:

152020

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0717

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00529

AC:

1331

AN:

251388

Hom.:

AF XY:

0.00397

AC XY:

540

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0722

Gnomad AMR exome

AF:

0.00335

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00205

AC:

2994

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1266

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0716

Gnomad4 AMR exome

AF:

0.00380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.00430

GnomAD4 genome

AF:

0.0209

AC:

3184

AN:

152138

Hom.:

119

Cov.:

AF XY:

0.0200

AC XY:

1491

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0718

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00363

Hom.:

Bravo

AF:

0.0236

ESP6500AA

AF:

0.0649

AC:

286

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00656

AC:

797

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.50

T;.

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.098

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.99

D;D

Vest4

0.17

MVP

0.45

MPC

0.22

ClinPred

0.057

GERP RS

-0.27

Varity_R

0.058

gMVP

0.24

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

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