chr1-177085635-A-C

Position:

• chr1-177085635-A-C

Variant summary

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

The NM_004319.3(ASTN1):​c.284-24370T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,990 control chromosomes in the GnomAD database, including 11,479 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 0.36 (11479 hom., cov: 31)
• Consequence: ASTN1 NM_004319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.284-24370T>G		intron_variant		ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.284-24370T>G		intron_variant		1	NM_004319.3	ENSP00000354536	P1
ASTN1	ENST00000367657.7	c.284-24370T>G		intron_variant		1		ENSP00000356629
ASTN1	ENST00000424564.2	c.284-24370T>G		intron_variant		1		ENSP00000395041
ASTN1	ENST00000281881.7	n.581-24370T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54686 AN: 151872 Hom.: 11476 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.360 AC: 54701 AN: 151990 Hom.: 11479 Cov.: 31 AF XY: 0.354 AC XY: 26296 AN XY: 74284

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.0138

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.348

Alfa AF: 0.443 Hom.: 30926

Bravo AF: 0.335

Asia WGS AF: 0.111 AC: 388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.63

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: rs6678480; hg19: chr1-177054771;