7-70617103-C-G

Variant names:

• chr7-70617103-C-G
• rs10263367
• NM_015570.4:c.691-81466C>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.691-81466C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,016 control chromosomes in the GnomAD database, including 21,760 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 0.53 (21760 hom., cov: 33)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• 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), 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.691-81466C>G		intron_variant	Intron 5 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.691-81466C>G		intron_variant	Intron 5 of 18	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000406775.6	c.691-81466C>G		intron_variant	Intron 5 of 17	1		ENSP00000385263.2
AUTS2	ENST00000644939.1	c.691-81466C>G		intron_variant	Intron 5 of 18			ENSP00000496726.1
AUTS2	ENST00000644506.1	c.-682+20304C>G		intron_variant	Intron 1 of 14			ENSP00000496672.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79813 AN: 151898 Hom.: 21725 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.526 AC: 79902 AN: 152016 Hom.: 21760 Cov.: 33 AF XY: 0.524 AC XY: 38966 AN XY: 74304

African (AFR) AF: 0.640 AC: 26522 AN: 41452

American (AMR) AF: 0.471 AC: 7203 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1965 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1452 AN: 5172

South Asian (SAS) AF: 0.371 AC: 1783 AN: 4810

European-Finnish (FIN) AF: 0.508 AC: 5364 AN: 10552

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33713 AN: 67964

Other (OTH) AF: 0.523 AC: 1104 AN: 2110

Alfa AF: 0.374 Hom.: 961

Bravo AF: 0.530

Asia WGS AF: 0.365 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.35
PhyloP100		-0.26
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: rs10263367; hg19: chr7-70082089;