rs56694150

chr2-174811388-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001822.7(CHN1):c.964+123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 592,952 control chromosomes in the GnomAD database, including 589 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 0.051 (321 hom., cov: 33)
  • Exomes 𝑓: 0.030 (268 hom.)
• Consequence: CHN1 NM_001822.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN1	NM_001822.7	c.964+123A>T		intron_variant		ENST00000409900.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN1	ENST00000409900.9	c.964+123A>T		intron_variant		1	NM_001822.7	P1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7755 AN: 152198 Hom.: 323 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0303 AC: 13361 AN: 440636 Hom.: 268 Cov.: 6 AF XY: 0.0296 AC XY: 6793 AN XY: 229138

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0318

Gnomad4 ASJ exome AF: 0.0589

Gnomad4 EAS exome AF: 0.000178

Gnomad4 SAS exome AF: 0.0240

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.0304

Gnomad4 OTH exome AF: 0.0384

GnomAD4 genome AF: 0.0510 AC: 7763 AN: 152316 Hom.: 321 Cov.: 33 AF XY: 0.0480 AC XY: 3572 AN XY: 74494

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0625

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0241

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0386 Hom.: 21

Bravo AF: 0.0552

Asia WGS AF: 0.0140 AC: 48 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.13
Dann	Benign	0.37

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: rs56694150; hg19: chr2-175676116;