rs10490693

Positions:

• chr2-164792667-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365672.2(COBLL1):​c.41+48489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,070 control chromosomes in the GnomAD database, including 1,413 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 0.12 (1413 hom., cov: 32)
• Consequence: COBLL1 NM_001365672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

Genes affected

COBLL1 (HGNC:23571): (cordon-bleu WH2 repeat protein like 1) Enables cadherin binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

COBLL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COBLL1	NM_001365672.2	c.41+48489C>T		intron_variant		ENST00000652658.2	NP_001352601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COBLL1	ENST00000652658.2	c.41+48489C>T		intron_variant			NM_001365672.2	ENSP00000498242.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17914 AN: 151952 Hom.: 1413 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.118 AC: 17913 AN: 152070 Hom.: 1413 Cov.: 32 AF XY: 0.118 AC XY: 8771 AN XY: 74326

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0678

Gnomad4 EAS AF: 0.0605

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.118

Alfa AF: 0.143 Hom.: 2111

Bravo AF: 0.114

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs10490693; hg19: chr2-165649177;