chr7-70294546-C-A

Variant names:

• chr7-70294546-C-A
• rs3846984
• NM_015570.4:c.661-141206C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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), Orphanet, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.661-141206C>A		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.661-141206C>A		intron	N/A	NP_001120703.1	Q8WXX7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.661-141206C>A		intron	N/A	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.661-141206C>A		intron	N/A	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000644939.1		c.661-141206C>A		intron	N/A	ENSP00000496726.1	A0A2R8Y8C6

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

African (AFR) AF: 0.437 AC: 18125 AN: 41430

American (AMR) AF: 0.286 AC: 4367 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1543 AN: 5174

South Asian (SAS) AF: 0.342 AC: 1643 AN: 4810

European-Finnish (FIN) AF: 0.244 AC: 2579 AN: 10588

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17621 AN: 67968

Other (OTH) AF: 0.333 AC: 705 AN: 2114

Alfa AF: 0.293 Hom.: 909

Bravo AF: 0.327

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.80
PhyloP100		4.1
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: rs3846984; hg19: chr7-69759532;