rs12328675

Variant names:

• chr2-164684290-T-C
• rs12328675
• NM_001365672.2:c.*1656A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 88 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365672.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBLL1	NM_001365672.2	MANE Select	c.*1656A>G		3_prime_UTR	Exon 14 of 14	NP_001352601.1	Q53SF7-4
	COBLL1	NM_001278458.2		c.*1656A>G		3_prime_UTR	Exon 17 of 17	NP_001265387.1	A0A0D9SG04
	COBLL1	NM_001278460.2		c.*1656A>G		3_prime_UTR	Exon 14 of 14	NP_001265389.1	A0A0X1KG75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBLL1	ENST00000652658.2	MANE Select	c.*1656A>G		3_prime_UTR	Exon 14 of 14	ENSP00000498242.1	Q53SF7-4
	COBLL1	ENST00000375458.6	TSL:1	c.*1656A>G		3_prime_UTR	Exon 13 of 13	ENSP00000364607.2	Q53SF7-4
	COBLL1	ENST00000926847.1		c.*1656A>G		3_prime_UTR	Exon 14 of 14	ENSP00000596906.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.156 AC: 6482 AN: 41512

American (AMR) AF: 0.114 AC: 1740 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 519 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5182

South Asian (SAS) AF: 0.102 AC: 494 AN: 4828

European-Finnish (FIN) AF: 0.0860 AC: 910 AN: 10576

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8541 AN: 67968

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.125 Hom.: 4572

Bravo AF: 0.129

Asia WGS AF: 0.0570 AC: 199 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.75
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12328675; hg19: chr2-165540800;