1-177023540-C-T

Position:

• chr1-177023540-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004319.3(ASTN1):​c.1302G>A​(p.Gln434=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,601,130 control chromosomes in the GnomAD database, including 134,863 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 0.35 (10033 hom., cov: 32)
  • Exomes 𝑓: 0.40 (124830 hom.)
• Consequence: ASTN1 NM_004319.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.735 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.1302G>A	p.Gln434=	synonymous_variant	7/23	ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.1302G>A	p.Gln434=	synonymous_variant	7/23	1	NM_004319.3	ENSP00000354536	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52897 AN: 151856 Hom.: 10030 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.00713

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.343 AC: 81568 AN: 237830 Hom.: 16241 AF XY: 0.352 AC XY: 45438 AN XY: 129074

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.00526

Gnomad SAS exome AF: 0.319

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.404 AC: 586039 AN: 1449156 Hom.: 124830 Cov.: 44 AF XY: 0.404 AC XY: 291279 AN XY: 720858

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.00237

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.348 AC: 52913 AN: 151974 Hom.: 10033 Cov.: 32 AF XY: 0.341 AC XY: 25356 AN XY: 74300

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.00734

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.357

Alfa AF: 0.384 Hom.: 5172

Bravo AF: 0.335

Asia WGS AF: 0.132 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.9
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10798496; hg19: chr1-176992676; COSMIC: COSV56069665;