rs10224955

Variant names:

• chr7-70532589-C-T
• rs10224955
• NM_015570.4:c.690+96808C>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.690+96808C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,204 control chromosomes in the GnomAD database, including 223 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 0.043 (223 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.690+96808C>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.690+96808C>T		intron_variant	Intron 5 of 18	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000406775.6	c.690+96808C>T		intron_variant	Intron 5 of 17	1		ENSP00000385263.2
AUTS2	ENST00000644939.1	c.690+96808C>T		intron_variant	Intron 5 of 18			ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6579 AN: 152086 Hom.: 219 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.00886

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0433 AC: 6587 AN: 152204 Hom.: 223 Cov.: 32 AF XY: 0.0424 AC XY: 3153 AN XY: 74410

African (AFR) AF: 0.0935 AC: 3883 AN: 41524

American (AMR) AF: 0.0419 AC: 641 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0223 AC: 107 AN: 4808

European-Finnish (FIN) AF: 0.00886 AC: 94 AN: 10606

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0248 AC: 1685 AN: 68018

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0328 Hom.: 144

Bravo AF: 0.0484

Asia WGS AF: 0.0180 AC: 62 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.80
PhyloP100		-2.1
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: rs10224955; hg19: chr7-69997575;