Genetic Variant CD101:p.Val839Ile (chr1-117025595-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001256106.3(CD101):c.2515G>A(p.Val839Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,613,910 control chromosomes in the GnomAD database, including 338 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.

Frequency

Genomes: 𝑓 0.014 ( 31 hom., cov: 32)

Exomes 𝑓: 0.018 ( 307 hom. )

Consequence

CD101
NM_001256106.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019327402).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0143 (2182/152340) while in subpopulation AMR AF = 0.0274 (419/15302). AF 95% confidence interval is 0.0252. There are 31 homozygotes in GnomAd4. There are 1132 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD101	NM_001256106.3 link	c.2515G>A	p.Val839Ile	missense_variant	Exon 8 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.2515G>A	p.Val839Ile	missense_variant	Exon 8 of 10		NM_001256106.3	ENSP00000508039.1		Q93033

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2184

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00371

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0177

AC:

4448

AN:

250864

AF XY:

0.0163

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.0414

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00185

Gnomad FIN exome

AF:

0.0342

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0183

AC:

26718

AN:

1461570

Hom.:

307

Cov.:

AF XY:

0.0177

AC XY:

12849

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.00287

AC:

AN:

33480

American (AMR)

AF:

0.0406

AC:

1818

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000957

AC:

AN:

26134

East Asian (EAS)

AF:

0.00209

AC:

AN:

39700

South Asian (SAS)

AF:

0.00248

AC:

214

AN:

86256

European-Finnish (FIN)

AF:

0.0336

AC:

1785

AN:

53144

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0196

AC:

21795

AN:

1111972

Other (OTH)

AF:

0.0148

AC:

892

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1479

2957

4436

5914

7393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

834

1668

2502

3336

4170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0143

AC:

2182

AN:

152340

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1132

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00370

AC:

154

AN:

41586

American (AMR)

AF:

0.0274

AC:

419

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00212

AC:

AN:

5188

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0387

AC:

411

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0170

AC:

1154

AN:

68032

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0146

TwinsUK

AF:

0.0213

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0183

AC:

157

ExAC

AF:

0.0163

AC:

1979

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0171

EpiControl

AF:

0.0151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.082

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.093

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.55

T;.

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PhyloP100

-1.7

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.032

Sift

Benign

0.40

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.042

B;B

Vest4

0.028

MPC

0.089

ClinPred

0.0056

GERP RS

-9.1

Varity_R

0.015

gMVP

0.045

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over