rs228014

Positions:

• chr1-177002472-T-C

Variant summary

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

The NM_004319.3(ASTN1):​c.1523+12319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,586 control chromosomes in the GnomAD database, including 25,682 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 0.58 (25682 hom., cov: 31)
• Consequence: ASTN1 NM_004319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN1	NM_004319.3	c.1523+12319A>G		intron_variant		ENST00000361833.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN1	ENST00000361833.7	c.1523+12319A>G		intron_variant		1	NM_004319.3	P1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87201 AN: 151468 Hom.: 25673 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.576 AC: 87244 AN: 151586 Hom.: 25682 Cov.: 31 AF XY: 0.570 AC XY: 42165 AN XY: 74038

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.538

Alfa AF: 0.588 Hom.: 3256

Bravo AF: 0.572

Asia WGS AF: 0.316 AC: 1102 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.066
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: rs228014; hg19: chr1-176971608; COSMIC: COSV56069278;