rs228008

Variant names:

• chr1-176994071-T-C
• rs228008
• NM_004319.3:c.1523+20720A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004319.3(ASTN1):​c.1523+20720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 149,888 control chromosomes in the GnomAD database, including 27,346 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 0.59 (27346 hom., cov: 27)
• Consequence: ASTN1 NM_004319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.1523+20720A>G		intron_variant	Intron 8 of 22	ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.1523+20720A>G		intron_variant	Intron 8 of 22	1	NM_004319.3	ENSP00000354536.2

Frequencies

GnomAD3 genomes AF: 0.595 AC: 89041 AN: 149774 Hom.: 27325 Cov.: 27

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.594 AC: 89098 AN: 149888 Hom.: 27346 Cov.: 27 AF XY: 0.587 AC XY: 42856 AN XY: 72956

African (AFR) AF: 0.715 AC: 28935 AN: 40466

American (AMR) AF: 0.501 AC: 7520 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3470

East Asian (EAS) AF: 0.194 AC: 994 AN: 5112

South Asian (SAS) AF: 0.439 AC: 2087 AN: 4754

European-Finnish (FIN) AF: 0.614 AC: 6119 AN: 9966

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39708 AN: 67818

Other (OTH) AF: 0.551 AC: 1154 AN: 2096

Alfa AF: 0.589 Hom.: 57064

Bravo AF: 0.595

Asia WGS AF: 0.327 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.8
DANN	Benign	0.62
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs228008; hg19: chr1-176963207;