Genetic Variant NM_020770.3: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CGN	NM_020770.3 link	c.1141-114T>C	intron_variant	Intron 5 of 20	ENST00000271636.12	NP_065821.1	Q9P2M7-1
CGN	XM_005245365.6 link	c.1141-114T>C	intron_variant	Intron 5 of 20		XP_005245422.1	Q9P2M7-1
CGN	XR_921902.3 link	n.1284-114T>C	intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGN	ENST00000271636.12 link	c.1141-114T>C		intron_variant	Intron 5 of 20	1	NM_020770.3	ENSP00000271636.7		Q9P2M7-1
CGN	ENST00000416743.1 link	c.265-114T>C		intron_variant	Intron 4 of 4	5		ENSP00000390686.1		H0Y4A8

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over