2-174799378-AAAGT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001822.7(CHN1):c.*734_*737del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 416,914 control chromosomes in the GnomAD database, including 2,889 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1069 hom., cov: 31)
  • Exomes 𝑓: 0.11 (1820 hom.)
• Consequence: CHN1 NM_001822.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.17

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-174799378-AAAGT-A is Benign according to our data. Variant chr2-174799378-AAAGT-A is described in ClinVar as [Likely_benign]. Clinvar id is 332453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN1	NM_001822.7	c.*734_*737del		3_prime_UTR_variant	13/13	ENST00000409900.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN1	ENST00000409900.9	c.*734_*737del		3_prime_UTR_variant	13/13	1	NM_001822.7	P1
CHN1	ENST00000295497.13	c.*734_*737del		3_prime_UTR_variant	7/7	1
CHN1	ENST00000652036.1	c.*734_*737del		3_prime_UTR_variant	8/8
CHN1	ENST00000443238.6			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18195 AN: 152080 Hom.: 1063 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.113 AC: 8041 AN: 71444 Hom.: 480 AF XY: 0.112 AC XY: 4302 AN XY: 38368

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.0778

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.0980

Gnomad SAS exome AF: 0.100

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.114 AC: 30104 AN: 264716 Hom.: 1820 AF XY: 0.113 AC XY: 16573 AN XY: 146704

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0784

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.0953

Gnomad4 FIN exome AF: 0.0860

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.120 AC: 18214 AN: 152198 Hom.: 1069 Cov.: 31 AF XY: 0.117 AC XY: 8705 AN XY: 74450

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0848

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0939

Gnomad4 FIN AF: 0.0909

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.129

Alfa AF: 0.118 Hom.: 148

Bravo AF: 0.122

Asia WGS AF: 0.103 AC: 356 AN: 3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Duane retraction syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs66480716; hg19: chr2-175664106;