NM_001365672.2:c.2701A>G

Variant names:

• chr2-164694691-T-C
• rs7607980
• NM_001365672.2:c.2701A>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.2701A>G​(p.Asn901Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,602 control chromosomes in the GnomAD database, including 11,983 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 (1281 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10702 hom.)
• Consequence: COBLL1 NM_001365672.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685
• Publications: 83 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 (MetaRNN=0.001427412).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 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.2701A>G	p.Asn901Asp	missense	Exon 12 of 14	NP_001352601.1
	COBLL1	NM_001278458.2		c.3016A>G	p.Asn1006Asp	missense	Exon 15 of 17	NP_001265387.1
	COBLL1	NM_001278460.2		c.2839A>G	p.Asn947Asp	missense	Exon 12 of 14	NP_001265389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBLL1	ENST00000652658.2	MANE Select	c.2701A>G	p.Asn901Asp	missense	Exon 12 of 14	ENSP00000498242.1
	COBLL1	ENST00000409184.8	TSL:1	c.2839A>G	p.Asn947Asp	missense	Exon 12 of 14	ENSP00000387326.5
	COBLL1	ENST00000342193.8	TSL:1	c.2815A>G	p.Asn939Asp	missense	Exon 12 of 14	ENSP00000341360.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19173 AN: 151800 Hom.: 1281 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.108 AC: 27042 AN: 250474 AF XY: 0.111

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0712

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.0939

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.118 AC: 172098 AN: 1461684 Hom.: 10702 Cov.: 34 AF XY: 0.118 AC XY: 86143 AN XY: 727134

African (AFR) AF: 0.159 AC: 5331 AN: 33468

American (AMR) AF: 0.0747 AC: 3335 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3834 AN: 26126

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39698

South Asian (SAS) AF: 0.109 AC: 9426 AN: 86250

European-Finnish (FIN) AF: 0.0983 AC: 5247 AN: 53392

Middle Eastern (MID) AF: 0.170 AC: 981 AN: 5756

European-Non Finnish (NFE) AF: 0.123 AC: 136570 AN: 1111932

Other (OTH) AF: 0.122 AC: 7362 AN: 60388

GnomAD4 genome AF: 0.126 AC: 19178 AN: 151918 Hom.: 1281 Cov.: 32 AF XY: 0.125 AC XY: 9292 AN XY: 74250

African (AFR) AF: 0.157 AC: 6497 AN: 41414

American (AMR) AF: 0.114 AC: 1729 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5164

South Asian (SAS) AF: 0.101 AC: 484 AN: 4806

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: 0.127 AC: 8608 AN: 67956

Other (OTH) AF: 0.128 AC: 270 AN: 2106

Alfa AF: 0.125 Hom.: 5993

Bravo AF: 0.129

TwinsUK AF: 0.119 AC: 442

ALSPAC AF: 0.131 AC: 504

ESP6500AA AF: 0.156 AC: 687

ESP6500EA AF: 0.125 AC: 1074

ExAC AF: 0.110 AC: 13349

Asia WGS AF: 0.0570 AC: 197 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.4
DANN	Benign	0.95
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.69
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.040
Sift	Benign	0.13	T
Sift4G	Benign	0.31	T
Polyphen		0.70	P
Vest4		0.054
MPC		0.063
ClinPred		0.0070	T
GERP RS		-2.6
Varity_R		0.093
gMVP		0.089
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: rs7607980; hg19: chr2-165551201; COSMIC: COSV52077297; COSMIC: COSV52077297;