rs10237317

Variant names:

• chr7-70580955-A-G
• rs10237317
• NM_015570.4:c.691-117614A>G

Variant summary

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

The NM_015570.4(AUTS2):​c.691-117614A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,038 control chromosomes in the GnomAD database, including 13,505 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 0.41 (13505 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.691-117614A>G		intron	N/A	NP_056385.1
	AUTS2	NM_001127231.3		c.691-117614A>G		intron	N/A	NP_001120703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.691-117614A>G		intron	N/A	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.691-117614A>G		intron	N/A	ENSP00000385263.2
	AUTS2	ENST00000644939.1		c.691-117614A>G		intron	N/A	ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62989 AN: 151920 Hom.: 13502 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.414 AC: 63012 AN: 152038 Hom.: 13505 Cov.: 32 AF XY: 0.419 AC XY: 31124 AN XY: 74310

African (AFR) AF: 0.344 AC: 14246 AN: 41468

American (AMR) AF: 0.448 AC: 6846 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3466 AN: 5150

South Asian (SAS) AF: 0.568 AC: 2741 AN: 4822

European-Finnish (FIN) AF: 0.405 AC: 4285 AN: 10570

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28686 AN: 67968

Other (OTH) AF: 0.426 AC: 898 AN: 2110

Alfa AF: 0.423 Hom.: 20375

Bravo AF: 0.413

Asia WGS AF: 0.564 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.87
PhyloP100		0.17
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: rs10237317; hg19: chr7-70045941;