rs13228123

Variant names:

• chr7-70127715-G-T
• rs13228123
• NM_015570.4:c.625-6821G>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.625-6821G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,990 control chromosomes in the GnomAD database, including 7,127 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 (7127 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.839
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.625-6821G>T		intron_variant	Intron 3 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.625-6821G>T		intron_variant	Intron 3 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45497 AN: 151872 Hom.: 7107 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.300 AC: 45564 AN: 151990 Hom.: 7127 Cov.: 32 AF XY: 0.302 AC XY: 22430 AN XY: 74296

African (AFR) AF: 0.376 AC: 15600 AN: 41450

American (AMR) AF: 0.274 AC: 4181 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3466

East Asian (EAS) AF: 0.296 AC: 1526 AN: 5152

South Asian (SAS) AF: 0.341 AC: 1641 AN: 4810

European-Finnish (FIN) AF: 0.252 AC: 2660 AN: 10560

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17666 AN: 67966

Other (OTH) AF: 0.318 AC: 672 AN: 2110

Alfa AF: 0.283 Hom.: 1044

Bravo AF: 0.304

Asia WGS AF: 0.337 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.40
PhyloP100		0.84
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: rs13228123; hg19: chr7-69592701;