Variant 1-176864291-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004319.3(ASTN1):c.3878A>G(p.Glu1293Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00333 in 1,613,990 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 21 hom. )

Consequence

ASTN1
NM_004319.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.30

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033033192).

BP6

Variant 1-176864291-T-C is Benign according to our data. Variant chr1-176864291-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2639585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ASTN1	NM_004319.3 linkuse as main transcript	c.3878A>G	p.Glu1293Gly	missense_variant	23/23	ENST00000361833.7
ASTN1	NM_001364856.2 linkuse as main transcript	c.3902A>G	p.Glu1301Gly	missense_variant	23/23
ASTN1	NM_001286164.2 linkuse as main transcript	c.3647+4553A>G		intron_variant
ASTN1	XM_017001341.3 linkuse as main transcript	c.3671+4553A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN1	ENST00000361833.7 linkuse as main transcript	c.3878A>G	p.Glu1293Gly	missense_variant	23/23	1	NM_004319.3	P1	O14525-2
ASTN1	ENST00000367657.7 linkuse as main transcript	c.3647+4553A>G		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

382

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00425

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00236

AC:

592

AN:

251024

Hom.:

AF XY:

0.00237

AC XY:

321

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.000602

Gnomad NFE exome

AF:

0.00392

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00341

AC:

4989

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2414

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00403

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.00251

AC:

382

AN:

152284

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00425

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.00258

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00232

AC:

282

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ASTN1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 13, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

ASTN1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.051

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

M_CAP

Benign

0.018

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.43

REVEL

Benign

0.087

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.022

Polyphen

0.24

Vest4

0.13

MVP

0.068

MPC

0.29

ClinPred

0.021

GERP RS

4.6

gMVP

0.44

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

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