rs956403

Positions:

• chr7-70602879-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015570.4(AUTS2):​c.691-95690C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,058 control chromosomes in the GnomAD database, including 6,491 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 0.29 (6491 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.691-95690C>A		intron_variant		ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.691-95690C>A		intron_variant		1	NM_015570.4	P4
AUTS2	ENST00000406775.6	c.691-95690C>A		intron_variant		1
AUTS2	ENST00000644506.1	c.-682+6080C>A		intron_variant
AUTS2	ENST00000644939.1	c.691-95690C>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43444 AN: 151940 Hom.: 6492 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.286 AC: 43474 AN: 152058 Hom.: 6491 Cov.: 32 AF XY: 0.281 AC XY: 20897 AN XY: 74334

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.0261

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.288

Alfa AF: 0.301 Hom.: 1523

Bravo AF: 0.284

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs956403; hg19: chr7-70067865;