2-164733949-C-T

Variant names:

• chr2-164733949-C-T
• rs7574791
• NM_001365672.2:c.231-3834G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365672.2(COBLL1):​c.231-3834G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,126 control chromosomes in the GnomAD database, including 1,909 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 0.15 (1909 hom., cov: 32)
• Consequence: COBLL1 NM_001365672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBLL1	NM_001365672.2	MANE Select	c.231-3834G>A		intron	N/A	NP_001352601.1
	COBLL1	NM_001278458.2		c.390-3834G>A		intron	N/A	NP_001265387.1
	COBLL1	NM_001278460.2		c.369-3834G>A		intron	N/A	NP_001265389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBLL1	ENST00000652658.2	MANE Select	c.231-3834G>A		intron	N/A	ENSP00000498242.1
	COBLL1	ENST00000409184.8	TSL:1	c.369-3834G>A		intron	N/A	ENSP00000387326.5
	COBLL1	ENST00000342193.8	TSL:1	c.231-3834G>A		intron	N/A	ENSP00000341360.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23222 AN: 152008 Hom.: 1898 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.153 AC: 23241 AN: 152126 Hom.: 1909 Cov.: 32 AF XY: 0.152 AC XY: 11281 AN XY: 74368

African (AFR) AF: 0.117 AC: 4875 AN: 41506

American (AMR) AF: 0.166 AC: 2541 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3466

East Asian (EAS) AF: 0.295 AC: 1522 AN: 5152

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4820

European-Finnish (FIN) AF: 0.0964 AC: 1022 AN: 10600

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10775 AN: 67988

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.164 Hom.: 1780

Bravo AF: 0.155

Asia WGS AF: 0.268 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7574791; hg19: chr2-165590459;