Variant chr2-174812294-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000409900.9(CHN1):c.886+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,596,542 control chromosomes in the GnomAD database, including 178,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 12129 hom., cov: 32)

Exomes 𝑓: 0.47 ( 166365 hom. )

Consequence

CHN1
ENST00000409900.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0350

Variant links:

Genes affected

CHN1 (HGNC:1943): (chimerin 1) This gene encodes GTPase-activating protein for ras-related p21-rac and a phorbol ester receptor. It is predominantly expressed in neurons, and plays an important role in neuronal signal-transduction mechanisms. Mutations in this gene are associated with Duane's retraction syndrome 2 (DURS2). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CHN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-174812294-C-T is Benign according to our data. Variant chr2-174812294-C-T is described in ClinVar as [Benign]. Clinvar id is 332464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN1	NM_001822.7 linkuse as main transcript	c.886+15G>A		intron_variant		ENST00000409900.9	NP_001813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN1	ENST00000409900.9 linkuse as main transcript	c.886+15G>A		intron_variant		1	NM_001822.7	ENSP00000386741	P1	P15882-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55351

AN:

151954

Hom.:

12137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.426

AC:

103784

AN:

243890

Hom.:

24087

AF XY:

0.440

AC XY:

58222

AN XY:

132174

show subpopulations

Gnomad AFR exome

AF:

0.0981

Gnomad AMR exome

AF:

0.246

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.459

Gnomad SAS exome

AF:

0.497

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.473

AC:

683267

AN:

1444470

Hom.:

166365

Cov.:

AF XY:

0.476

AC XY:

340547

AN XY:

716138

show subpopulations

Gnomad4 AFR exome

AF:

0.0936

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.490

Gnomad4 FIN exome

AF:

0.473

Gnomad4 NFE exome

AF:

0.496

Gnomad4 OTH exome

AF:

0.456

GnomAD4 genome

AF:

0.364

AC:

55336

AN:

152072

Hom.:

12129

Cov.:

AF XY:

0.365

AC XY:

27153

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.428

Hom.:

2953

Bravo

AF:

0.339

Asia WGS

AF:

0.476

AC:

1657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Duane retraction syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.1

DANN

Benign

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over