1-151518550-C-T

Position:

• chr1-151518550-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000271636.12(CGN):​c.31C>T​(p.Arg11Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,610,464 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (26 hom.)
• Consequence: CGN ENST00000271636.12 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.370

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065971613).
• BP6: Variant 1-151518550-C-T is Benign according to our data. Variant chr1-151518550-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 730505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-151518550-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00173 (2517/1458262) while in subpopulation MID AF= 0.0191 (110/5756). AF 95% confidence interval is 0.0162. There are 26 homozygotes in gnomad4_exome. There are 1269 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGN	NM_020770.3	c.31C>T	p.Arg11Trp	missense_variant	2/21	ENST00000271636.12	NP_065821.1
CGN	XM_005245365.6	c.31C>T	p.Arg11Trp	missense_variant	2/21		XP_005245422.1
CGN	XR_921902.3	n.174C>T		non_coding_transcript_exon_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGN	ENST00000271636.12	c.31C>T	p.Arg11Trp	missense_variant	2/21	1	NM_020770.3	ENSP00000271636	P1
CGN	ENST00000502442.1	c.31C>T	p.Arg11Trp	missense_variant	2/2	1		ENSP00000422299
CGN	ENST00000505188.5	c.31C>T	p.Arg11Trp	missense_variant	2/2	1		ENSP00000425532
CGN	ENST00000427934.2	c.31C>T	p.Arg11Trp	missense_variant	3/3	5		ENSP00000410836

Frequencies

GnomAD3 genomes AF: 0.00199 AC: 302 AN: 152084 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.0335

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00275 AC: 687 AN: 250230 Hom.: 4 AF XY: 0.00275 AC XY: 372 AN XY: 135232

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00415

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000851

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00165

Gnomad OTH exome AF: 0.00706

GnomAD4 exome AF: 0.00173 AC: 2517 AN: 1458262 Hom.: 26 Cov.: 32 AF XY: 0.00175 AC XY: 1269 AN XY: 724618

Gnomad4 AFR exome AF: 0.000479

Gnomad4 AMR exome AF: 0.00437

Gnomad4 ASJ exome AF: 0.0298

Gnomad4 EAS exome AF: 0.0000758

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000982

Gnomad4 OTH exome AF: 0.00399

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152202 Hom.: 5 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74416

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.0335

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00308 Hom.: 9

Bravo AF: 0.00224

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00267 AC: 23

ExAC AF: 0.00278 AC: 338

EpiCase AF: 0.00338

EpiControl AF: 0.00302

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	CGN: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	.;.;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.77	.;T;T;.
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.0066	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D;D;N;N
REVEL	Benign	0.14
Sift	Benign	0.031	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Vest4		0.37
MVP		0.54
MPC		0.64
ClinPred		0.071	T
GERP RS		1.9
gMVP		0.18

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: rs144766457; hg19: chr1-151491026;