rs771199357

Variant names:

• chr2-174799860-G-A
• rs771199357
• NM_001822.7:c.*256C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-174799860-G-A
• chr2-174799860-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BS1_Supporting BS2

The NM_001822.7(CHN1):​c.*256C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000265 in 592,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: CHN1 NM_001822.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000276 (42/152212) while in subpopulation NFE AF = 0.000544 (37/68028). AF 95% confidence interval is 0.000405. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 42 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.*256C>T		3_prime_UTR	Exon 13 of 13	NP_001813.1	P15882-1
	CHN1	NM_001371514.1		c.*256C>T		3_prime_UTR	Exon 13 of 13	NP_001358443.1
	CHN1	NM_001371513.1		c.*256C>T		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.*256C>T		3_prime_UTR	Exon 13 of 13	ENSP00000386741.4	P15882-1
	CHN1	ENST00000295497.13	TSL:1	c.*256C>T		3_prime_UTR	Exon 7 of 7	ENSP00000295497.7	P15882-2
	CHN1	ENST00000488080.6	TSL:1	n.1279C>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000544

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000217 AC: 29 AN: 133552 AF XY: 0.000261

Gnomad AFR exome AF: 0.000160

Gnomad AMR exome AF: 0.0000411

Gnomad ASJ exome AF: 0.000122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000457

Gnomad OTH exome AF: 0.000245

GnomAD4 exome AF: 0.000261 AC: 115 AN: 440048 Hom.: 0 Cov.: 3 AF XY: 0.000263 AC XY: 63 AN XY: 239466

African (AFR) AF: 0.0000719 AC: 1 AN: 13910

American (AMR) AF: 0.0000318 AC: 1 AN: 31416

Ashkenazi Jewish (ASJ) AF: 0.0000575 AC: 1 AN: 17378

East Asian (EAS) AF: 0.00 AC: 0 AN: 23834

South Asian (SAS) AF: 0.0000493 AC: 3 AN: 60882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1966

European-Non Finnish (NFE) AF: 0.000428 AC: 106 AN: 247852

Other (OTH) AF: 0.000123 AC: 3 AN: 24352

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74380

African (AFR) AF: 0.0000965 AC: 4 AN: 41448

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000855 Hom.: 0

Bravo AF: 0.000268

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	-0.38
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		6.7

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: rs771199357; hg19: chr2-175664588;