Variant chr1-176864344-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004319.3(ASTN1):c.3825G>A(p.Thr1275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,614,124 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 18 hom. )

Consequence

ASTN1
NM_004319.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.44

Variant links:

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]

ASTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 1-176864344-C-T is Benign according to our data. Variant chr1-176864344-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639586.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-8.44 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ASTN1	NM_004319.3 linkuse as main transcript	c.3825G>A	p.Thr1275=	synonymous_variant	23/23	ENST00000361833.7
ASTN1	NM_001364856.2 linkuse as main transcript	c.3849G>A	p.Thr1283=	synonymous_variant	23/23
ASTN1	NM_001286164.2 linkuse as main transcript	c.3647+4500G>A		intron_variant
ASTN1	XM_017001341.3 linkuse as main transcript	c.3671+4500G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN1	ENST00000361833.7 linkuse as main transcript	c.3825G>A	p.Thr1275=	synonymous_variant	23/23	1	NM_004319.3	P1	O14525-2
ASTN1	ENST00000367657.7 linkuse as main transcript	c.3647+4500G>A		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

419

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00352

AC:

885

AN:

251236

Hom.:

AF XY:

0.00384

AC XY:

522

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00745

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.00398

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00384

AC:

5611

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

2880

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00976

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00714

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.00392

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.00275

AC:

419

AN:

152262

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.00251

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

ASTN1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

1.9

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over