rs6943555

Variant names:

• chr7-70341037-T-A
• rs6943555
• NM_015570.4:c.661-94715T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015570.4(AUTS2):​c.661-94715T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,068 control chromosomes in the GnomAD database, including 10,144 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 (10144 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 58 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.661-94715T>A		intron_variant	Intron 4 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.661-94715T>A		intron_variant	Intron 4 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51700 AN: 151950 Hom.: 10100 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.341 AC: 51793 AN: 152068 Hom.: 10144 Cov.: 32 AF XY: 0.342 AC XY: 25428 AN XY: 74348

African (AFR) AF: 0.545 AC: 22583 AN: 41468

American (AMR) AF: 0.291 AC: 4446 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1799 AN: 5160

South Asian (SAS) AF: 0.342 AC: 1650 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2464 AN: 10594

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16587 AN: 67964

Other (OTH) AF: 0.340 AC: 716 AN: 2106

Alfa AF: 0.271 Hom.: 3338

Bravo AF: 0.355

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.31
PhyloP100		-0.015
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: rs6943555; hg19: chr7-69806023;