rs210606

Positions:

• chr7-69769942-G-A

Variant summary

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

The NM_015570.4(AUTS2):​c.310-129344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,056 control chromosomes in the GnomAD database, including 11,687 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 0.39 (11687 hom., cov: 33)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.310-129344G>A		intron_variant		ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.310-129344G>A		intron_variant		1	NM_015570.4	ENSP00000344087	P4

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58714 AN: 151938 Hom.: 11661 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.387 AC: 58784 AN: 152056 Hom.: 11687 Cov.: 33 AF XY: 0.389 AC XY: 28878 AN XY: 74332

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.387

Alfa AF: 0.358 Hom.: 4577

Bravo AF: 0.391

Asia WGS AF: 0.359 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.51

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: rs210606; hg19: chr7-69234928;