dbSNP rs172917: ASTN1:p.Cys475Cys (chr1-177023417-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004319.3(ASTN1):c.1425T>C(p.Cys475Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,592,448 control chromosomes in the GnomAD database, including 282,406 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 0.61 ( 29542 hom., cov: 30)

Exomes 𝑓: 0.59 ( 252864 hom. )

Consequence

ASTN1
NM_004319.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.371

Publications

17 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-0.371 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3 link	c.1425T>C	p.Cys475Cys	synonymous_variant	Exon 7 of 23	ENST00000361833.7	NP_004310.1	A6H8Y4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7 link	c.1425T>C	p.Cys475Cys	synonymous_variant	Exon 7 of 23	1	NM_004319.3	ENSP00000354536.2		O14525-2

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93195

AN:

151786

Hom.:

29519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.576

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.579

GnomAD2 exomes

AF:

0.536

AC:

116973

AN:

218168

AF XY:

0.535

show subpopulations

Gnomad AFR exome

AF:

0.738

Gnomad AMR exome

AF:

0.449

Gnomad ASJ exome

AF:

0.560

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.594

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.586

AC:

843564

AN:

1440544

Hom.:

252864

Cov.:

AF XY:

0.583

AC XY:

416632

AN XY:

715018

show subpopulations

African (AFR)

AF:

0.746

AC:

24356

AN:

32628

American (AMR)

AF:

0.458

AC:

18974

AN:

41416

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

14482

AN:

25588

East Asian (EAS)

AF:

0.166

AC:

6419

AN:

38756

South Asian (SAS)

AF:

0.475

AC:

39573

AN:

83350

European-Finnish (FIN)

AF:

0.635

AC:

33197

AN:

52248

Middle Eastern (MID)

AF:

0.616

AC:

3528

AN:

5726

European-Non Finnish (NFE)

AF:

0.607

AC:

668585

AN:

1101380

Other (OTH)

AF:

0.579

AC:

34450

AN:

59452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

18508

37016

55524

74032

92540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18040

36080

54120

72160

90200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.614

AC:

93260

AN:

151904

Hom.:

29542

Cov.:

AF XY:

0.608

AC XY:

45107

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.740

AC:

30655

AN:

41436

American (AMR)

AF:

0.511

AC:

7800

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

2000

AN:

3470

East Asian (EAS)

AF:

0.199

AC:

1024

AN:

5148

South Asian (SAS)

AF:

0.450

AC:

2148

AN:

4776

European-Finnish (FIN)

AF:

0.643

AC:

6785

AN:

10558

Middle Eastern (MID)

AF:

0.582

AC:

170

AN:

292

European-Non Finnish (NFE)

AF:

0.603

AC:

40998

AN:

67950

Other (OTH)

AF:

0.573

AC:

1211

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1706

3412

5118

6824

8530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.600

Hom.:

114300

Bravo

AF:

0.611

Asia WGS

AF:

0.338

AC:

1180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.87

(source)

DANN

Benign

0.48

PhyloP100

-0.37

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over