rs6460557

Variant names:

• chr7-70776312-A-G
• rs6460557
• NM_015570.4:c.1933-791A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-70776312-A-G
• chr7-70776312-A-T

Variant summary

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

The NM_015570.4(AUTS2):​c.1933-791A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,068 control chromosomes in the GnomAD database, including 3,407 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 0.19 (3407 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 0 publications found

Genes affected

AUTS2 (HGNC:14262): (activator of transcription and developmental regulator AUTS2) This gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. Mutations in this gene have also been associated with non-neurological disorders, such as acute lymphoblastic leukemia, aging of the skin, early-onset androgenetic alopecia, and certain cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2014]

AUTS2 Gene-Disease associations (from GenCC):

• autism spectrum disorder due to AUTS2 deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.1933-791A>G		intron_variant	Intron 13 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.1933-791A>G		intron_variant	Intron 13 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29578 AN: 151950 Hom.: 3393 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0984

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.195 AC: 29631 AN: 152068 Hom.: 3407 Cov.: 32 AF XY: 0.200 AC XY: 14835 AN XY: 74316

African (AFR) AF: 0.285 AC: 11837 AN: 41472

American (AMR) AF: 0.205 AC: 3140 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 341 AN: 3464

East Asian (EAS) AF: 0.382 AC: 1964 AN: 5138

South Asian (SAS) AF: 0.157 AC: 759 AN: 4820

European-Finnish (FIN) AF: 0.244 AC: 2581 AN: 10578

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8464 AN: 67990

Other (OTH) AF: 0.187 AC: 396 AN: 2116

Alfa AF: 0.149 Hom.: 4158

Bravo AF: 0.201

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.54
PhyloP100		-1.2
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: rs6460557; hg19: chr7-70241298;