dbSNP rs56694150: CHN1:c.964+123A>T (chr2-174811388-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001822.7(CHN1):c.964+123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 592,952 control chromosomes in the GnomAD database, including 589 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 0.051 ( 321 hom., cov: 33)

Exomes 𝑓: 0.030 ( 268 hom. )

Consequence

CHN1
NM_001822.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.330

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN1	NM_001822.7 link	c.964+123A>T		intron_variant	Intron 10 of 12	ENST00000409900.9	NP_001813.1	P15882-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHN1	ENST00000409900.9 link	c.964+123A>T		intron_variant	Intron 10 of 12	1	NM_001822.7	ENSP00000386741.4		P15882-1

Frequencies

GnomAD3 genomes

AF:

0.0510

AC:

7755

AN:

152198

Hom.:

323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.0625

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0540

GnomAD4 exome

AF:

0.0303

AC:

13361

AN:

440636

Hom.:

268

Cov.:

AF XY:

0.0296

AC XY:

6793

AN XY:

229138

show subpopulations

African (AFR)

AF:

0.105

AC:

1158

AN:

11078

American (AMR)

AF:

0.0318

AC:

432

AN:

13572

Ashkenazi Jewish (ASJ)

AF:

0.0589

AC:

762

AN:

12940

East Asian (EAS)

AF:

0.000178

AC:

AN:

28022

South Asian (SAS)

AF:

0.0240

AC:

687

AN:

28590

European-Finnish (FIN)

AF:

0.0185

AC:

778

AN:

41950

Middle Eastern (MID)

AF:

0.0613

AC:

182

AN:

2968

European-Non Finnish (NFE)

AF:

0.0304

AC:

8415

AN:

277002

Other (OTH)

AF:

0.0384

AC:

942

AN:

24514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

606

1212

1817

2423

3029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.0510

AC:

7763

AN:

152316

Hom.:

321

Cov.:

AF XY:

0.0480

AC XY:

3572

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.108

AC:

4488

AN:

41546

American (AMR)

AF:

0.0388

AC:

593

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0625

AC:

217

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.0241

AC:

116

AN:

4822

European-Finnish (FIN)

AF:

0.0126

AC:

134

AN:

10622

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0305

AC:

2073

AN:

68038

Other (OTH)

AF:

0.0535

AC:

113

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

362

725

1087

1450

1812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0386

Hom.:

Bravo

AF:

0.0552

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.13

(source)

DANN

Benign

0.37

PhyloP100

-0.33

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over