2-174809142-C-T

Variant names:

• chr2-174809142-C-T
• rs57776382
• NM_001822.7:c.965-100G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001822.7(CHN1):​c.965-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 1,101,730 control chromosomes in the GnomAD database, including 771 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 0.047 (258 hom., cov: 33)
  • Exomes 𝑓: 0.029 (513 hom.)
• Consequence: CHN1 NM_001822.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 3 publications found

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

ENSG00000236449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0923 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN1	NM_001822.7	MANE Select	c.965-100G>A		intron	N/A	NP_001813.1	P15882-1
	CHN1	NM_001371514.1		c.1016-100G>A		intron	N/A	NP_001358443.1
	CHN1	NM_001371513.1		c.965-100G>A		intron	N/A	NP_001358442.1	P15882-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN1	ENST00000409900.9	TSL:1 MANE Select	c.965-100G>A		intron	N/A	ENSP00000386741.4	P15882-1
	CHN1	ENST00000295497.13	TSL:1	c.590-100G>A		intron	N/A	ENSP00000295497.7	P15882-2
	CHN1	ENST00000488080.6	TSL:1	n.608-100G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7120 AN: 152038 Hom.: 259 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0613

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.0508

GnomAD4 exome AF: 0.0288 AC: 27393 AN: 949574 Hom.: 513 AF XY: 0.0286 AC XY: 13474 AN XY: 471468

African (AFR) AF: 0.0915 AC: 1966 AN: 21482

American (AMR) AF: 0.0279 AC: 513 AN: 18412

Ashkenazi Jewish (ASJ) AF: 0.0584 AC: 964 AN: 16498

East Asian (EAS) AF: 0.0000899 AC: 3 AN: 33368

South Asian (SAS) AF: 0.0229 AC: 1098 AN: 47936

European-Finnish (FIN) AF: 0.0189 AC: 754 AN: 39992

Middle Eastern (MID) AF: 0.0688 AC: 208 AN: 3024

European-Non Finnish (NFE) AF: 0.0281 AC: 20425 AN: 727122

Other (OTH) AF: 0.0350 AC: 1462 AN: 41740

GnomAD4 genome AF: 0.0469 AC: 7129 AN: 152156 Hom.: 258 Cov.: 33 AF XY: 0.0442 AC XY: 3286 AN XY: 74386

African (AFR) AF: 0.0948 AC: 3934 AN: 41498

American (AMR) AF: 0.0367 AC: 562 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0613 AC: 213 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4814

European-Finnish (FIN) AF: 0.0127 AC: 134 AN: 10576

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0299 AC: 2036 AN: 67998

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

Alfa AF: 0.0224 Hom.: 16

Bravo AF: 0.0508

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.1
DANN	Benign	0.83
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57776382; hg19: chr2-175673870;