chr2-174799439-C-T

Variant names:

• chr2-174799439-C-T
• rs192645480
• NM_001822.7:c.*677G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001822.7(CHN1):​c.*677G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0113 in 462,550 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (12 hom., cov: 33)
  • Exomes 𝑓: 0.012 (46 hom.)
• Consequence: CHN1 NM_001822.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.00
• Publications: 2 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=-0.28).
• BP6: Variant 2-174799439-C-T is Benign according to our data. Variant chr2-174799439-C-T is described in ClinVar as Benign. ClinVar VariationId is 332455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00882 (1341/152118) while in subpopulation SAS AF = 0.0152 (73/4818). AF 95% confidence interval is 0.0124. There are 12 homozygotes in GnomAd4. There are 617 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1341 AD gene.

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.*677G>A		3_prime_UTR	Exon 13 of 13	NP_001813.1	P15882-1
	CHN1	NM_001371514.1		c.*677G>A		3_prime_UTR	Exon 13 of 13	NP_001358443.1
	CHN1	NM_001371513.1		c.*677G>A		3_prime_UTR	Exon 14 of 14	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.*677G>A		3_prime_UTR	Exon 13 of 13	ENSP00000386741.4	P15882-1
	CHN1	ENST00000295497.13	TSL:1	c.*677G>A		3_prime_UTR	Exon 7 of 7	ENSP00000295497.7	P15882-2
	CHN1	ENST00000934192.1		c.*677G>A		3_prime_UTR	Exon 14 of 14	ENSP00000604251.1

Frequencies

GnomAD3 genomes AF: 0.00883 AC: 1342 AN: 152002 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.0114 AC: 1133 AN: 99158 AF XY: 0.0116

Gnomad AFR exome AF: 0.00127

Gnomad AMR exome AF: 0.00987

Gnomad ASJ exome AF: 0.0390

Gnomad EAS exome AF: 0.000117

Gnomad FIN exome AF: 0.00224

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.0161

GnomAD4 exome AF: 0.0125 AC: 3867 AN: 310432 Hom.: 46 Cov.: 0 AF XY: 0.0128 AC XY: 2199 AN XY: 171266

African (AFR) AF: 0.00199 AC: 17 AN: 8530

American (AMR) AF: 0.0100 AC: 183 AN: 18216

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 518 AN: 12170

East Asian (EAS) AF: 0.000120 AC: 2 AN: 16730

South Asian (SAS) AF: 0.0150 AC: 778 AN: 51790

European-Finnish (FIN) AF: 0.00310 AC: 35 AN: 11278

Middle Eastern (MID) AF: 0.0319 AC: 40 AN: 1252

European-Non Finnish (NFE) AF: 0.0117 AC: 2040 AN: 174024

Other (OTH) AF: 0.0154 AC: 254 AN: 16442

GnomAD4 genome AF: 0.00882 AC: 1341 AN: 152118 Hom.: 12 Cov.: 33 AF XY: 0.00830 AC XY: 617 AN XY: 74366

African (AFR) AF: 0.00212 AC: 88 AN: 41480

American (AMR) AF: 0.0125 AC: 191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0152 AC: 73 AN: 4818

European-Finnish (FIN) AF: 0.00293 AC: 31 AN: 10572

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 755 AN: 68006

Other (OTH) AF: 0.0180 AC: 38 AN: 2114

Alfa AF: 0.00871 Hom.: 7

Bravo AF: 0.00929

Asia WGS AF: 0.00578 AC: 20 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Duane retraction syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		5.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs192645480; hg19: chr2-175664167;