rs12669427

Variant names:

• chr7-70667961-C-T
• rs12669427
• NM_015570.4:c.691-30608C>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.691-30608C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,010 control chromosomes in the GnomAD database, including 19,295 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 (19295 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.691-30608C>T		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.691-30608C>T		intron_variant	Intron 5 of 18	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000406775.6	c.691-30608C>T		intron_variant	Intron 5 of 17	1		ENSP00000385263.2
AUTS2	ENST00000644939.1	c.691-30608C>T		intron_variant	Intron 5 of 18			ENSP00000496726.1
AUTS2	ENST00000644506.1	c.-681-30608C>T		intron_variant	Intron 1 of 14			ENSP00000496672.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74713 AN: 151892 Hom.: 19263 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.492 AC: 74804 AN: 152010 Hom.: 19295 Cov.: 32 AF XY: 0.499 AC XY: 37045 AN XY: 74312

African (AFR) AF: 0.642 AC: 26623 AN: 41448

American (AMR) AF: 0.486 AC: 7419 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3468

East Asian (EAS) AF: 0.500 AC: 2578 AN: 5158

South Asian (SAS) AF: 0.490 AC: 2362 AN: 4816

European-Finnish (FIN) AF: 0.504 AC: 5320 AN: 10566

Middle Eastern (MID) AF: 0.483 AC: 139 AN: 288

European-Non Finnish (NFE) AF: 0.397 AC: 26952 AN: 67972

Other (OTH) AF: 0.472 AC: 995 AN: 2110

Alfa AF: 0.442 Hom.: 7516

Bravo AF: 0.500

Asia WGS AF: 0.504 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.68
PhyloP100		0.16
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: rs12669427; hg19: chr7-70132947;