dbSNP rs17229382: CD101:p.Val839Ile (chr1-117025595-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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. 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.

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

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 -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

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	UniProt
CD101	ENST00000682167.1 link	c.2515G>A	p.Val839Ile	missense_variant	Exon 8 of 10		NM_001256106.3	ENSP00000508039.1	Q93033
CD101	ENST00000369470.1 link	c.2515G>A	p.Val839Ile	missense_variant	Exon 8 of 10	1		ENSP00000358482.1	Q93033
CD101	ENST00000256652.8 link	c.2515G>A	p.Val839Ile	missense_variant	Exon 8 of 9	2		ENSP00000256652.4	Q93033
CD101-AS1	ENST00000445523.1 link	n.1701C>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

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

GnomAD3 exomes

AF:

0.0177

AC:

4448

AN:

250864

Hom.:

AF XY:

0.0163

AC XY:

2206

AN XY:

135572

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 SAS exome

AF:

0.00232

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

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.0406

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00209

Gnomad4 SAS exome

AF:

0.00248

Gnomad4 FIN exome

AF:

0.0336

Gnomad4 NFE exome

AF:

0.0196

Gnomad4 OTH exome

AF:

0.0148

GnomAD4 genome

AF:

0.0143

AC:

2182

AN:

152340

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1132

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00370

Gnomad4 AMR

AF:

0.0274

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0170

Gnomad4 OTH

AF:

0.0109

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over