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GeneBe

1-176864344-C-T

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

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.44 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASTN1NM_004319.3 linkuse as main transcriptc.3825G>A p.Thr1275= synonymous_variant 23/23 ENST00000361833.7
ASTN1NM_001364856.2 linkuse as main transcriptc.3849G>A p.Thr1283= synonymous_variant 23/23
ASTN1NM_001286164.2 linkuse as main transcriptc.3647+4500G>A intron_variant
ASTN1XM_017001341.3 linkuse as main transcriptc.3671+4500G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASTN1ENST00000361833.7 linkuse as main transcriptc.3825G>A p.Thr1275= synonymous_variant 23/231 NM_004319.3 P1O14525-2
ASTN1ENST00000367657.7 linkuse as main transcriptc.3647+4500G>A intron_variant 1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00275
AC:
419
AN:
152144
Hom.:
4
Cov.:
32
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.:
5
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.:
18
Cov.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00275
AC:
419
AN:
152262
Hom.:
4
Cov.:
32
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.:
1
Bravo
AF:
0.00251
Asia WGS
AF:
0.00260
AC:
9
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2023ASTN1: 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.

Other links and lift over

dbSNP: rs144824957; hg19: chr1-176833480; COSMIC: COSV62490495; COSMIC: COSV62490495; API