Genetic Variant CHN1:c.886+15G>A (chr2-174812294-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001822.7(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
NM_001822.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0350

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

Duane retraction syndrome 2
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
Duane retraction syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CHN1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001822.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHN1	NM_001822.7	MANE Select	c.886+15G>A	intron	N/A	NP_001813.1	P15882-1
CHN1	NM_001371514.1		c.937+15G>A	intron	N/A	NP_001358443.1
CHN1	NM_001371513.1		c.886+15G>A	intron	N/A	NP_001358442.1	P15882-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHN1	ENST00000409900.9	TSL:1 MANE Select	c.886+15G>A	intron	N/A	ENSP00000386741.4	P15882-1
CHN1	ENST00000295497.13	TSL:1	c.511+15G>A	intron	N/A	ENSP00000295497.7	P15882-2
CHN1	ENST00000488080.6	TSL:1	n.529+15G>A	intron	N/A

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

GnomAD2 exomes

AF:

0.426

AC:

103784

AN:

243890

AF XY:

0.440

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 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

African (AFR)

AF:

0.0936

AC:

3109

AN:

33228

American (AMR)

AF:

0.256

AC:

11312

AN:

44110

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

10324

AN:

25534

East Asian (EAS)

AF:

0.439

AC:

17318

AN:

39410

South Asian (SAS)

AF:

0.490

AC:

40967

AN:

83566

European-Finnish (FIN)

AF:

0.473

AC:

25034

AN:

52976

Middle Eastern (MID)

AF:

0.443

AC:

2509

AN:

5662

European-Non Finnish (NFE)

AF:

0.496

AC:

545512

AN:

1100410

Other (OTH)

AF:

0.456

AC:

27182

AN:

59574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

16208

32416

48625

64833

81041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15872

31744

47616

63488

79360

<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:

0.364

AC:

55336

AN:

152072

Hom.:

12129

Cov.:

AF XY:

0.365

AC XY:

27153

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.109

AC:

4543

AN:

41508

American (AMR)

AF:

0.316

AC:

4832

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1444

AN:

3468

East Asian (EAS)

AF:

0.450

AC:

2325

AN:

5170

South Asian (SAS)

AF:

0.495

AC:

2388

AN:

4820

European-Finnish (FIN)

AF:

0.472

AC:

4983

AN:

10556

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.491

AC:

33375

AN:

67952

Other (OTH)

AF:

0.379

AC:

799

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1609

3217

4826

6434

8043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.440

Hom.:

7812

Bravo

AF:

0.339

Asia WGS

AF:

0.476

AC:

1657

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Duane retraction syndrome 2 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.1

(source)

DANN

Benign

0.38

PhyloP100

0.035

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over