dbSNP rs2337359: CGN:c.1141-114T>C (chr1-151523320-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020770.3(CGN):c.1141-114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 940,396 control chromosomes in the GnomAD database, including 39,199 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 0.31 ( 9260 hom., cov: 33)

Exomes 𝑓: 0.23 ( 29939 hom. )

Consequence

CGN
NM_020770.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Publications

7 publications found

Variant links:

Genes affected

CGN (HGNC:17429): (cingulin) Enables cadherin binding activity. Predicted to act upstream of or within bicellular tight junction assembly; epithelial cell morphogenesis; and microtubule cytoskeleton organization. Located in bicellular tight junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CGN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020770.3. 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
	CGN	NM_020770.3	MANE Select	c.1141-114T>C		intron	N/A	NP_065821.1	Q9P2M7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CGN	ENST00000271636.12	TSL:1 MANE Select	c.1141-114T>C	intron	N/A	ENSP00000271636.7	Q9P2M7-1
CGN	ENST00000879040.1		c.1141-114T>C	intron	N/A	ENSP00000549099.1
CGN	ENST00000879038.1		c.1141-114T>C	intron	N/A	ENSP00000549097.1

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46686

AN:

152074

Hom.:

9252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.232

AC:

183111

AN:

788204

Hom.:

29939

AF XY:

0.231

AC XY:

92755

AN XY:

401070

show subpopulations

African (AFR)

AF:

0.478

AC:

9223

AN:

19308

American (AMR)

AF:

0.480

AC:

11442

AN:

23834

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

2379

AN:

15354

East Asian (EAS)

AF:

0.790

AC:

27085

AN:

34292

South Asian (SAS)

AF:

0.300

AC:

14821

AN:

49352

European-Finnish (FIN)

AF:

0.245

AC:

11475

AN:

46842

Middle Eastern (MID)

AF:

0.184

AC:

755

AN:

4100

European-Non Finnish (NFE)

AF:

0.174

AC:

97046

AN:

558924

Other (OTH)

AF:

0.245

AC:

8885

AN:

36198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6152

12305

18457

24610

30762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3148

6296

9444

12592

15740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.307

AC:

46724

AN:

152192

Hom.:

9260

Cov.:

AF XY:

0.316

AC XY:

23485

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.466

AC:

19343

AN:

41504

American (AMR)

AF:

0.393

AC:

6009

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

566

AN:

3470

East Asian (EAS)

AF:

0.805

AC:

4172

AN:

5184

South Asian (SAS)

AF:

0.316

AC:

1524

AN:

4828

European-Finnish (FIN)

AF:

0.256

AC:

2707

AN:

10590

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11756

AN:

68006

Other (OTH)

AF:

0.274

AC:

579

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1531

3062

4592

6123

7654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.270

Hom.:

1386

Bravo

AF:

0.329

Asia WGS

AF:

0.496

AC:

1723

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.16

(source)

DANN

Benign

0.41

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over