2-174799439-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001822.7(CHN1):c.*677G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0113 in 462,550 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0088 ( 12 hom., cov: 33)

Exomes 𝑓: 0.012 ( 46 hom. )

Consequence

CHN1
NM_001822.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.00

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 2-174799439-C-T is Benign according to our data. Variant chr2-174799439-C-T is described in ClinVar as [Benign]. Clinvar id is 332455.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00882 (1341/152118) while in subpopulation SAS AF= 0.0152 (73/4818). AF 95% confidence interval is 0.0124. There are 12 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd at 1342 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN1	NM_001822.7 linkuse as main transcript	c.*677G>A		3_prime_UTR_variant	13/13	ENST00000409900.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN1	ENST00000409900.9 linkuse as main transcript	c.*677G>A	3_prime_UTR_variant	13/13	1	NM_001822.7	P1	P15882-1
CHN1	ENST00000295497.13 linkuse as main transcript	c.*677G>A	3_prime_UTR_variant	7/7	1			P15882-2
CHN1	ENST00000443238.6 linkuse as main transcript	c.*677G>A	3_prime_UTR_variant	8/8	4
CHN1	ENST00000652036.1 linkuse as main transcript	c.*677G>A	3_prime_UTR_variant	8/8

Frequencies

GnomAD3 genomes

AF:

0.00883

AC:

1342

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.0433

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0114

AC:

1133

AN:

99158

Hom.:

AF XY:

0.0116

AC XY:

631

AN XY:

54554

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.00987

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.000117

Gnomad SAS exome

AF:

0.0134

Gnomad FIN exome

AF:

0.00224

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.0125

AC:

3867

AN:

310432

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

2199

AN XY:

171266

show subpopulations

Gnomad4 AFR exome

AF:

0.00199

Gnomad4 AMR exome

AF:

0.0100

Gnomad4 ASJ exome

AF:

0.0426

Gnomad4 EAS exome

AF:

0.000120

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.00310

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.00882

AC:

1341

AN:

152118

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

617

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.0125

Gnomad4 ASJ

AF:

0.0433

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0152

Gnomad4 FIN

AF:

0.00293

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00929

Asia WGS

AF:

0.00578

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Duane retraction syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.92

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