rs73968220

Variant names:

• chr2-164685954-C-G
• rs73968220
• NM_001365672.2:c.3379G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-164685954-C-G
• chr2-164685954-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365672.2(COBLL1):​c.3379G>C​(p.Gly1127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,600,894 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1127S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: COBLL1 NM_001365672.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035486817).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.3379G>C	p.Gly1127Arg	missense	Exon 14 of 14	NP_001352601.1	Q53SF7-4
	COBLL1	NM_001278458.2		c.3694G>C	p.Gly1232Arg	missense	Exon 17 of 17	NP_001265387.1	A0A0D9SG04
	COBLL1	NM_001278460.2		c.3517G>C	p.Gly1173Arg	missense	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.3379G>C	p.Gly1127Arg	missense	Exon 14 of 14	ENSP00000498242.1	Q53SF7-4
	COBLL1	ENST00000409184.8	TSL:1	c.3517G>C	p.Gly1173Arg	missense	Exon 14 of 14	ENSP00000387326.5	A0A0X1KG75
	COBLL1	ENST00000342193.8	TSL:1	c.3493G>C	p.Gly1165Arg	missense	Exon 14 of 14	ENSP00000341360.4	Q53SF7-3

Frequencies

GnomAD3 genomes AF: 0.00287 AC: 437 AN: 152008 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000717 AC: 178 AN: 248164 AF XY: 0.000528

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.000385

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000262 AC: 380 AN: 1448768 Hom.: 1 Cov.: 27 AF XY: 0.000227 AC XY: 164 AN XY: 721654

African (AFR) AF: 0.00975 AC: 322 AN: 33030

American (AMR) AF: 0.000521 AC: 23 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101586

Other (OTH) AF: 0.000501 AC: 30 AN: 59904

GnomAD4 genome AF: 0.00288 AC: 438 AN: 152126 Hom.: 2 Cov.: 32 AF XY: 0.00285 AC XY: 212 AN XY: 74366

African (AFR) AF: 0.0100 AC: 417 AN: 41512

American (AMR) AF: 0.000983 AC: 15 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.00320

ESP6500AA AF: 0.00999 AC: 44

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000848 AC: 103

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.20
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.063
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.089	T
Polyphen		0.94	P
Vest4		0.085
MVP		0.27
MPC		0.32
ClinPred		0.049	T
GERP RS		-1.8
Varity_R		0.12
gMVP		0.19
Mutation Taster		=99/1	polymorphism

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: rs73968220; hg19: chr2-165542464;