rs3846984

Positions:

• chr7-70294546-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015570.4(AUTS2):​c.661-141206C>A variant causes a intron change. The variant allele was found at a frequency of 0.317 in 152,040 control chromosomes in the GnomAD database, including 8,151 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 0.32 (8151 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.661-141206C>A		intron_variant		ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.661-141206C>A		intron_variant		1	NM_015570.4	P4
AUTS2	ENST00000406775.6	c.661-141206C>A		intron_variant		1
AUTS2	ENST00000644939.1	c.661-141206C>A		intron_variant				A1
AUTS2	ENST00000643060.1	n.17-141206C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48130 AN: 151920 Hom.: 8130 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.317 AC: 48198 AN: 152040 Hom.: 8151 Cov.: 32 AF XY: 0.319 AC XY: 23677 AN XY: 74324

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.333

Alfa AF: 0.288 Hom.: 836

Bravo AF: 0.327

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.80

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: rs3846984; hg19: chr7-69759532;