2-174809142-C-T

Position:

• chr2-174809142-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN1	NM_001822.7	c.965-100G>A		intron_variant		ENST00000409900.9	NP_001813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN1	ENST00000409900.9	c.965-100G>A		intron_variant		1	NM_001822.7	ENSP00000386741.4

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

Gnomad4 AFR exome AF: 0.0915

Gnomad4 AMR exome AF: 0.0279

Gnomad4 ASJ exome AF: 0.0584

Gnomad4 EAS exome AF: 0.0000899

Gnomad4 SAS exome AF: 0.0229

Gnomad4 FIN exome AF: 0.0189

Gnomad4 NFE exome AF: 0.0281

Gnomad4 OTH exome AF: 0.0350

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

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0613

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0239

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0209 Hom.: 14

Bravo AF: 0.0508

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.1
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs57776382; hg19: chr2-175673870;