NM_015570.4:c.1469-306C>T

Variant names:

• chr7-70765808-C-T
• rs6960426
• NM_015570.4:c.1469-306C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015570.4(AUTS2):​c.1469-306C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,008 control chromosomes in the GnomAD database, including 21,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (21308 hom., cov: 31)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.586
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-70765808-C-T is Benign according to our data. Variant chr7-70765808-C-T is described in ClinVar as Benign. ClinVar VariationId is 1288508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 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.1469-306C>T		intron	N/A	NP_056385.1
	AUTS2	NM_001127231.3		c.1469-306C>T		intron	N/A	NP_001120703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.1469-306C>T		intron	N/A	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.1469-306C>T		intron	N/A	ENSP00000385263.2
	AUTS2	ENST00000644939.1		c.1466-306C>T		intron	N/A	ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76386 AN: 151888 Hom.: 21300 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.503 AC: 76416 AN: 152008 Hom.: 21308 Cov.: 31 AF XY: 0.506 AC XY: 37611 AN XY: 74304

African (AFR) AF: 0.250 AC: 10370 AN: 41466

American (AMR) AF: 0.567 AC: 8657 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1983 AN: 5150

South Asian (SAS) AF: 0.497 AC: 2399 AN: 4824

European-Finnish (FIN) AF: 0.693 AC: 7330 AN: 10574

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.619 AC: 42065 AN: 67934

Other (OTH) AF: 0.532 AC: 1124 AN: 2114

Alfa AF: 0.583 Hom.: 13636

Bravo AF: 0.485

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		0.59
PromoterAI		-0.018	Neutral
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: rs6960426; hg19: chr7-70230794;