7-70256281-T-C

Position:

• chr7-70256281-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.660+121710T>C		intron_variant		ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.660+121710T>C		intron_variant		1	NM_015570.4	ENSP00000344087	P4

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

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.320

Alfa AF: 0.273 Hom.: 944

Bravo AF: 0.306

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.6
DANN	Benign	0.78

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: rs6969375; hg19: chr7-69721267;