7-70744651-A-G

Variant names:

• chr7-70744651-A-G
• rs723340
• NM_015570.4:c.743-18219A>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.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
• Publications: 6 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

LOC105375347 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.743-18219A>G		intron	N/A	NP_056385.1
	AUTS2	NM_001127231.3		c.743-18219A>G		intron	N/A	NP_001120703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.743-18219A>G		intron	N/A	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.743-18219A>G		intron	N/A	ENSP00000385263.2
	AUTS2	ENST00000644939.1		c.743-18219A>G		intron	N/A	ENSP00000496726.1

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

African (AFR) AF: 0.769 AC: 31925 AN: 41500

American (AMR) AF: 0.493 AC: 7527 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1260 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3977 AN: 5142

South Asian (SAS) AF: 0.460 AC: 2216 AN: 4814

European-Finnish (FIN) AF: 0.295 AC: 3129 AN: 10590

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23043 AN: 67952

Other (OTH) AF: 0.481 AC: 1013 AN: 2108

Alfa AF: 0.374 Hom.: 16388

Bravo AF: 0.523

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.28
PhyloP100		-0.22
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: rs723340; hg19: chr7-70209637;