rs12130298

chr1-117001709-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The 1-117001709-A-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 1,130,562 control chromosomes in the GnomAD database, including 2,405 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (266 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2139 hom.)
• Consequence: CD101 ENST00000256652.8 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD101	ENST00000256652.8			upstream_gene_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7467 AN: 152148 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0773

Gnomad OTH AF: 0.0334

GnomAD4 exome AF: 0.0600 AC: 58716 AN: 978296 Hom.: 2139 Cov.: 13 AF XY: 0.0590 AC XY: 29763 AN XY: 504128

Gnomad4 AFR exome AF: 0.00946

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.0271

Gnomad4 EAS exome AF: 0.0000815

Gnomad4 SAS exome AF: 0.00712

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0715

Gnomad4 OTH exome AF: 0.0515

GnomAD4 genome AF: 0.0490 AC: 7467 AN: 152266 Hom.: 266 Cov.: 32 AF XY: 0.0493 AC XY: 3671 AN XY: 74448

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0997

Gnomad4 NFE AF: 0.0773

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0655 Hom.: 185

Bravo AF: 0.0401

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	18
Dann	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12130298; hg19: chr1-117544331; COSMIC: COSV56718118;