rs17229382

Variant names:

• chr1-117025595-G-A
• rs17229382
• NM_001256106.3:c.2515G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 10 publications found

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

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256106.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD101	NM_001256106.3	MANE Select	c.2515G>A	p.Val839Ile	missense	Exon 8 of 10	NP_001243035.1
	CD101	NM_001256109.3		c.2515G>A	p.Val839Ile	missense	Exon 8 of 10	NP_001243038.1
	CD101	NM_004258.6		c.2515G>A	p.Val839Ile	missense	Exon 8 of 10	NP_004249.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD101	ENST00000682167.1	MANE Select	c.2515G>A	p.Val839Ile	missense	Exon 8 of 10	ENSP00000508039.1
	CD101	ENST00000369470.1	TSL:1	c.2515G>A	p.Val839Ile	missense	Exon 8 of 10	ENSP00000358482.1
	CD101	ENST00000256652.8	TSL:2	c.2515G>A	p.Val839Ile	missense	Exon 8 of 9	ENSP00000256652.4

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2184 AN: 152222 Hom.: 31 Cov.: 32

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

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.: 31 AF XY: 0.0177 AC XY: 12849 AN XY: 727088

African (AFR) AF: 0.00287 AC: 96 AN: 33480

American (AMR) AF: 0.0406 AC: 1818 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000957 AC: 25 AN: 26134

East Asian (EAS) AF: 0.00209 AC: 83 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: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0196 AC: 21795 AN: 1111972

Other (OTH) AF: 0.0148 AC: 892 AN: 60392

GnomAD4 genome AF: 0.0143 AC: 2182 AN: 152340 Hom.: 31 Cov.: 32 AF XY: 0.0152 AC XY: 1132 AN XY: 74488

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: 4 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.0387 AC: 411 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0170 AC: 1154 AN: 68032

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.0153 Hom.: 81

Bravo AF: 0.0146

TwinsUK AF: 0.0213 AC: 79

ALSPAC AF: 0.0228 AC: 88

ESP6500AA AF: 0.00409 AC: 18

ESP6500EA AF: 0.0183 AC: 157

ExAC AF: 0.0163 AC: 1979

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.0171

EpiControl AF: 0.0151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.082
DANN	Benign	0.57
DEOGEN2	Benign	0.093	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.7
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.032
Sift	Benign	0.40	T
Sift4G	Benign	0.44	T
Polyphen		0.042	B
Vest4		0.028
MPC		0.089
ClinPred		0.0056	T
GERP RS		-9.1
Varity_R		0.015
gMVP		0.045
Mutation Taster		=100/0	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: rs17229382; hg19: chr1-117568217;