chr7-69692281-C-T

Variant names:

• chr7-69692281-C-T
• rs611052
• NM_015570.4:c.309+92319C>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.309+92319C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,092 control chromosomes in the GnomAD database, including 38,657 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 0.71 (38657 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.309+92319C>T		intron_variant	Intron 1 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.309+92319C>T		intron_variant	Intron 1 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108283 AN: 151974 Hom.: 38625 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.712 AC: 108361 AN: 152092 Hom.: 38657 Cov.: 32 AF XY: 0.709 AC XY: 52680 AN XY: 74352

African (AFR) AF: 0.746 AC: 30959 AN: 41480

American (AMR) AF: 0.669 AC: 10225 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2260 AN: 3468

East Asian (EAS) AF: 0.780 AC: 4041 AN: 5178

South Asian (SAS) AF: 0.674 AC: 3243 AN: 4814

European-Finnish (FIN) AF: 0.694 AC: 7325 AN: 10560

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47878 AN: 67982

Other (OTH) AF: 0.696 AC: 1472 AN: 2114

Alfa AF: 0.656 Hom.: 3569

Bravo AF: 0.714

Asia WGS AF: 0.719 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.63
PhyloP100		-1.3
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: rs611052; hg19: chr7-69157267;