NM_015570.4:c.523-43978G>A

Variant names:

• chr7-70074154-G-A
• rs6949651
• NM_015570.4:c.523-43978G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015570.4(AUTS2):​c.523-43978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,080 control chromosomes in the GnomAD database, including 8,897 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 0.34 (8897 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.523-43978G>A		intron_variant	Intron 2 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.523-43978G>A		intron_variant	Intron 2 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51283 AN: 151962 Hom.: 8879 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.338 AC: 51347 AN: 152080 Hom.: 8897 Cov.: 32 AF XY: 0.339 AC XY: 25200 AN XY: 74332

African (AFR) AF: 0.389 AC: 16112 AN: 41468

American (AMR) AF: 0.292 AC: 4464 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1552 AN: 5184

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4818

European-Finnish (FIN) AF: 0.309 AC: 3268 AN: 10566

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21804 AN: 67988

Other (OTH) AF: 0.349 AC: 738 AN: 2112

Alfa AF: 0.237 Hom.: 701

Bravo AF: 0.338

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.63
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: rs6949651; hg19: chr7-69539140;