rs172917

Positions:

• chr1-177023417-A-G
• chr1-177023417-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004319.3(ASTN1):​c.1425T>C​(p.Cys475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,592,448 control chromosomes in the GnomAD database, including 282,406 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 0.61 (29542 hom., cov: 30)
  • Exomes 𝑓: 0.59 (252864 hom.)
• Consequence: ASTN1 NM_004319.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

Genes affected

ASTN1 (HGNC:773): (astrotactin 1) Astrotactin is a neuronal adhesion molecule required for glial-guided migration of young postmitotic neuroblasts in cortical regions of developing brain, including cerebrum, hippocampus, cerebellum, and olfactory bulb (Fink et al., 1995).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.371 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN1	NM_004319.3	c.1425T>C	p.Cys475=	synonymous_variant	7/23	ENST00000361833.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN1	ENST00000361833.7	c.1425T>C	p.Cys475=	synonymous_variant	7/23	1	NM_004319.3	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93195 AN: 151786 Hom.: 29519 Cov.: 30

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.579

GnomAD3 exomes AF: 0.536 AC: 116973 AN: 218168 Hom.: 33142 AF XY: 0.535 AC XY: 62993 AN XY: 117674

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.449

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.462

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.586 AC: 843564 AN: 1440544 Hom.: 252864 Cov.: 57 AF XY: 0.583 AC XY: 416632 AN XY: 715018

Gnomad4 AFR exome AF: 0.746

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.579

GnomAD4 genome AF: 0.614 AC: 93260 AN: 151904 Hom.: 29542 Cov.: 30 AF XY: 0.608 AC XY: 45107 AN XY: 74216

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.573

Alfa AF: 0.596 Hom.: 53295

Bravo AF: 0.611

Asia WGS AF: 0.338 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.87
DANN	Benign	0.48

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: rs172917; hg19: chr1-176992553;