rs6668092

Variant names:

• chr1-177011455-T-C
• rs6668092
• NM_004319.3:c.1523+3336A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004319.3(ASTN1):​c.1523+3336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,856 control chromosomes in the GnomAD database, including 22,726 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 0.54 (22726 hom., cov: 31)
• Consequence: ASTN1 NM_004319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.1523+3336A>G		intron_variant	Intron 8 of 22	ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.1523+3336A>G		intron_variant	Intron 8 of 22	1	NM_004319.3	ENSP00000354536.2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82151 AN: 151734 Hom.: 22725 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.520

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82175 AN: 151856 Hom.: 22726 Cov.: 31 AF XY: 0.537 AC XY: 39823 AN XY: 74198

African (AFR) AF: 0.531 AC: 21965 AN: 41346

American (AMR) AF: 0.471 AC: 7189 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1023 AN: 5156

South Asian (SAS) AF: 0.438 AC: 2102 AN: 4800

European-Finnish (FIN) AF: 0.623 AC: 6567 AN: 10548

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39689 AN: 67970

Other (OTH) AF: 0.514 AC: 1084 AN: 2108

Alfa AF: 0.556 Hom.: 3999

Bravo AF: 0.532

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.57
PhyloP100		-0.018
Mutation Taster		=100/0	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: rs6668092; hg19: chr1-176980591; COSMIC: COSV56083336;