rs2337359

Positions:

• chr1-151523320-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGN	NM_020770.3	c.1141-114T>C		intron_variant		ENST00000271636.12	NP_065821.1
CGN	XM_005245365.6	c.1141-114T>C		intron_variant			XP_005245422.1
CGN	XR_921902.3	n.1284-114T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGN	ENST00000271636.12	c.1141-114T>C		intron_variant		1	NM_020770.3	ENSP00000271636	P1
CGN	ENST00000416743.1	c.267-114T>C		intron_variant		5		ENSP00000390686

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46686 AN: 152074 Hom.: 9252 Cov.: 33

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

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.307 AC: 46724 AN: 152192 Hom.: 9260 Cov.: 33 AF XY: 0.316 AC XY: 23485 AN XY: 74420

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.274

Alfa AF: 0.266 Hom.: 1305

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
DANN	Benign	0.41

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

LitVar

Other links and lift over

dbSNP: rs2337359; hg19: chr1-151495796; COSMIC: COSV54969631; COSMIC: COSV54969631;