7-70765808-C-T

Position:

• chr7-70765808-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.1469-306C>T		intron_variant		ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.1469-306C>T		intron_variant		1	NM_015570.4	ENSP00000344087.4

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

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.532

Alfa AF: 0.584 Hom.: 12178

Bravo AF: 0.485

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.6
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs6960426; hg19: chr7-70230794;