1-177023417-A-G

Variant names:

• chr1-177023417-A-G
• rs172917
• NM_004319.3:c.1425T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 17 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004319.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN1	NM_004319.3	MANE Select	c.1425T>C	p.Cys475Cys	synonymous	Exon 7 of 23	NP_004310.1
	ASTN1	NM_001364856.2		c.1425T>C	p.Cys475Cys	synonymous	Exon 7 of 23	NP_001351785.1
	ASTN1	NM_001286164.2		c.1425T>C	p.Cys475Cys	synonymous	Exon 7 of 23	NP_001273093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN1	ENST00000361833.7	TSL:1 MANE Select	c.1425T>C	p.Cys475Cys	synonymous	Exon 7 of 23	ENSP00000354536.2
	ASTN1	ENST00000367657.7	TSL:1	c.1425T>C	p.Cys475Cys	synonymous	Exon 7 of 23	ENSP00000356629.3
	ASTN1	ENST00000424564.2	TSL:1	c.1425T>C	p.Cys475Cys	synonymous	Exon 7 of 22	ENSP00000395041.2

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93195 AN: 151786 Hom.: 29519 Cov.: 30

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

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.: 57 AF XY: 0.583 AC XY: 416632 AN XY: 715018

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

GnomAD4 genome AF: 0.614 AC: 93260 AN: 151904 Hom.: 29542 Cov.: 30 AF XY: 0.608 AC XY: 45107 AN XY: 74216

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.87
DANN	Benign	0.48
PhyloP100		-0.37
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

dbSNP: rs172917; hg19: chr1-176992553; COSMIC: COSV107273579;