2-164670077-G-C

Variant names:

• chr2-164670077-G-C
• rs13432797
• NM_001365671.1:c.3478-4176C>G

Variant summary

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

The NM_001365671.1(COBLL1):​c.3478-4176C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,976 control chromosomes in the GnomAD database, including 14,154 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 0.40 (14154 hom., cov: 32)
• Consequence: COBLL1 NM_001365671.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COBLL1	NM_001365671.1	c.3478-4176C>G		intron_variant	Intron 14 of 15		NP_001352600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COBLL1	ENST00000495084.1	n.127-4176C>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61121 AN: 151858 Hom.: 14112 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.403 AC: 61200 AN: 151976 Hom.: 14154 Cov.: 32 AF XY: 0.394 AC XY: 29304 AN XY: 74286

African (AFR) AF: 0.637 AC: 26381 AN: 41444

American (AMR) AF: 0.285 AC: 4351 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1077 AN: 3468

East Asian (EAS) AF: 0.0703 AC: 363 AN: 5162

South Asian (SAS) AF: 0.200 AC: 965 AN: 4814

European-Finnish (FIN) AF: 0.305 AC: 3225 AN: 10568

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23597 AN: 67920

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.246 Hom.: 577

Bravo AF: 0.415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.42
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs13432797; hg19: chr2-165526587;