1-177047232-A-G

Position:

• chr1-177047232-A-G

Variant summary

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

The NM_004319.3(ASTN1):​c.471+13846T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,106 control chromosomes in the GnomAD database, including 22,770 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 0.54 (22770 hom., cov: 32)
• Consequence: ASTN1 NM_004319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN1	NM_004319.3	c.471+13846T>C		intron_variant		ENST00000361833.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN1	ENST00000361833.7	c.471+13846T>C		intron_variant		1	NM_004319.3	P1
ASTN1	ENST00000367657.7	c.471+13846T>C		intron_variant		1
ASTN1	ENST00000424564.2	c.471+13846T>C		intron_variant		1
ASTN1	ENST00000281881.7	n.768+13846T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82214 AN: 151986 Hom.: 22747 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82278 AN: 152106 Hom.: 22770 Cov.: 32 AF XY: 0.535 AC XY: 39791 AN XY: 74342

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.523

Alfa AF: 0.547 Hom.: 22638

Bravo AF: 0.541

Asia WGS AF: 0.336 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.084
DANN	Benign	0.36

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: rs6667588; hg19: chr1-177016368;