7-70744651-A-G

Position:

• chr7-70744651-A-G

Variant summary

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

The NM_015570.4(AUTS2):​c.743-18219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,048 control chromosomes in the GnomAD database, including 21,255 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 0.49 (21255 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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]

LOC105375347 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.743-18219A>G		intron_variant		ENST00000342771.10
LOC105375347	XR_927653.4	n.5613A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.743-18219A>G		intron_variant		1	NM_015570.4	P4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74419 AN: 151930 Hom.: 21191 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.490 AC: 74550 AN: 152048 Hom.: 21255 Cov.: 32 AF XY: 0.488 AC XY: 36233 AN XY: 74310

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.481

Alfa AF: 0.354 Hom.: 11396

Bravo AF: 0.523

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.28

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: rs723340; hg19: chr7-70209637;