rs10490694

Positions:

• chr2-164692059-G-A
• chr2-164692059-G-T

Variant summary

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

The NM_001365672.2(COBLL1):​c.3300+162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,136 control chromosomes in the GnomAD database, including 1,333 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 0.13 (1333 hom., cov: 32)
• Consequence: COBLL1 NM_001365672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COBLL1	NM_001365672.2	c.3300+162C>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.3300+162C>T		intron_variant			NM_001365672.2	ENSP00000498242	A2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19482 AN: 152018 Hom.: 1333 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.128 AC: 19488 AN: 152136 Hom.: 1333 Cov.: 32 AF XY: 0.127 AC XY: 9469 AN XY: 74378

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.129

Alfa AF: 0.123 Hom.: 1501

Bravo AF: 0.131

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.60

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: rs10490694; hg19: chr2-165548569;