rs369718610

Variant names:

• chr2-174799448-A-C
• rs369718610
• NM_001822.7:c.*668T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-174799448-A-C
• chr2-174799448-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001822.7(CHN1):​c.*668T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000855 in 467,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000095 (0 hom.)
• Consequence: CHN1 NM_001822.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).

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.*668T>G		3_prime_UTR	Exon 13 of 13	NP_001813.1	P15882-1
	CHN1	NM_001371514.1		c.*668T>G		3_prime_UTR	Exon 13 of 13	NP_001358443.1
	CHN1	NM_001371513.1		c.*668T>G		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.*668T>G		3_prime_UTR	Exon 13 of 13	ENSP00000386741.4	P15882-1
	CHN1	ENST00000295497.13	TSL:1	c.*668T>G		3_prime_UTR	Exon 7 of 7	ENSP00000295497.7	P15882-2
	CHN1	ENST00000934192.1		c.*668T>G		3_prime_UTR	Exon 14 of 14	ENSP00000604251.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152272 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000951 AC: 3 AN: 315384 Hom.: 0 Cov.: 0 AF XY: 0.00000576 AC XY: 1 AN XY: 173666

African (AFR) AF: 0.00 AC: 0 AN: 8786

American (AMR) AF: 0.00 AC: 0 AN: 18808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12486

East Asian (EAS) AF: 0.00 AC: 0 AN: 16998

South Asian (SAS) AF: 0.00 AC: 0 AN: 52332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1296

European-Non Finnish (NFE) AF: 0.0000170 AC: 3 AN: 176550

Other (OTH) AF: 0.00 AC: 0 AN: 16776

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74394

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68054

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		3.9

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: rs369718610; hg19: chr2-175664176;