rs12328675

chr2-164684290-T-C

Variant summary

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

The NM_001365672.2(COBLL1):c.*1656A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,120 control chromosomes in the GnomAD database, including 1,274 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 (1274 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: COBLL1 NM_001365672.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COBLL1	NM_001365672.2	c.*1656A>G		3_prime_UTR_variant	14/14	ENST00000652658.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COBLL1	ENST00000652658.2	c.*1656A>G		3_prime_UTR_variant	14/14		NM_001365672.2	A2
COBLL1	ENST00000375458.6	c.*1656A>G		3_prime_UTR_variant	13/13	1		A2
COBLL1	ENST00000495084.1	n.126+7931A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19110 AN: 152002 Hom.: 1274 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.128

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.126 AC: 19114 AN: 152120 Hom.: 1274 Cov.: 32 AF XY: 0.125 AC XY: 9294 AN XY: 74350

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0860

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.127

Alfa AF: 0.125 Hom.: 2169

Bravo AF: 0.129

Asia WGS AF: 0.0570 AC: 199 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.42
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12328675; hg19: chr2-165540800;