rs10235781

Variant names:

• chr7-70141950-A-G
• rs10235781
• NM_015570.4:c.660+7379A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-70141950-A-G
• chr7-70141950-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015570.4(AUTS2):​c.660+7379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,104 control chromosomes in the GnomAD database, including 7,188 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 0.30 (7188 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 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.660+7379A>G		intron	N/A	NP_056385.1
	AUTS2	NM_001127231.3		c.660+7379A>G		intron	N/A	NP_001120703.1
	AUTS2	NM_001127232.3		c.660+7379A>G		intron	N/A	NP_001120704.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.660+7379A>G		intron	N/A	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.660+7379A>G		intron	N/A	ENSP00000385263.2
	AUTS2	ENST00000403018.3	TSL:1	c.660+7379A>G		intron	N/A	ENSP00000385572.2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45708 AN: 151986 Hom.: 7168 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.301 AC: 45775 AN: 152104 Hom.: 7188 Cov.: 32 AF XY: 0.303 AC XY: 22553 AN XY: 74358

African (AFR) AF: 0.379 AC: 15706 AN: 41470

American (AMR) AF: 0.276 AC: 4214 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1540 AN: 5170

South Asian (SAS) AF: 0.341 AC: 1643 AN: 4816

European-Finnish (FIN) AF: 0.252 AC: 2671 AN: 10582

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

European-Non Finnish (NFE) AF: 0.260 AC: 17705 AN: 67996

Other (OTH) AF: 0.320 AC: 675 AN: 2110

Alfa AF: 0.278 Hom.: 1018

Bravo AF: 0.306

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.41
PhyloP100		0.022
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: rs10235781; hg19: chr7-69606936;