7-70256281-T-C

Variant names:

• chr7-70256281-T-C
• rs6969375
• NM_015570.4:c.660+121710T>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.660+121710T>C 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 152,068 control chromosomes in the GnomAD database, including 7,116 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 (7116 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.787
• 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.660+121710T>C		intron	N/A	NP_056385.1
	AUTS2	NM_001127231.3		c.660+121710T>C		intron	N/A	NP_001120703.1
	AUTS2	NM_001127232.3		c.661-34087T>C		intron	N/A	NP_001120704.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.660+121710T>C		intron	N/A	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.660+121710T>C		intron	N/A	ENSP00000385263.2
	AUTS2	ENST00000403018.3	TSL:1	c.661-34087T>C		intron	N/A	ENSP00000385572.2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45587 AN: 151950 Hom.: 7098 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.300 AC: 45651 AN: 152068 Hom.: 7116 Cov.: 32 AF XY: 0.303 AC XY: 22504 AN XY: 74332

African (AFR) AF: 0.369 AC: 15296 AN: 41456

American (AMR) AF: 0.278 AC: 4246 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1390 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1794 AN: 5172

South Asian (SAS) AF: 0.343 AC: 1649 AN: 4812

European-Finnish (FIN) AF: 0.252 AC: 2665 AN: 10582

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17704 AN: 67994

Other (OTH) AF: 0.320 AC: 673 AN: 2106

Alfa AF: 0.276 Hom.: 998

Bravo AF: 0.306

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.6
DANN	Benign	0.78
PhyloP100		0.79
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: rs6969375; hg19: chr7-69721267;