rs734930

Variant names:

• chr7-70555174-T-C
• rs734930
• NM_015570.4:c.690+119393T>C

Variant summary

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

The NM_015570.4(AUTS2):​c.690+119393T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,012 control chromosomes in the GnomAD database, including 21,652 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 0.53 (21652 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 9 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

LOC124901669 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.690+119393T>C		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.690+119393T>C		intron_variant	Intron 5 of 18	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000406775.6	c.690+119393T>C		intron_variant	Intron 5 of 17	1		ENSP00000385263.2
AUTS2	ENST00000644939.1	c.690+119393T>C		intron_variant	Intron 5 of 18			ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79896 AN: 151894 Hom.: 21623 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.526 AC: 79979 AN: 152012 Hom.: 21652 Cov.: 32 AF XY: 0.530 AC XY: 39399 AN XY: 74286

African (AFR) AF: 0.449 AC: 18614 AN: 41468

American (AMR) AF: 0.598 AC: 9127 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1567 AN: 5154

South Asian (SAS) AF: 0.400 AC: 1923 AN: 4806

European-Finnish (FIN) AF: 0.688 AC: 7271 AN: 10564

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37873 AN: 67968

Other (OTH) AF: 0.545 AC: 1151 AN: 2110

Alfa AF: 0.543 Hom.: 95631

Bravo AF: 0.520

Asia WGS AF: 0.395 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.72
DANN	Benign	0.69
PhyloP100		-0.041
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: rs734930; hg19: chr7-70020160;