7-69598673-T-C

Position:

• chr7-69598673-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_015570.4(AUTS2):​c.-981T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 159,586 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 30)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: AUTS2 NM_015570.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.378

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=-0.43).
• BP6: Variant 7-69598673-T-C is Benign according to our data. Variant chr7-69598673-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1199522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00374 (569/152136) while in subpopulation AFR AF= 0.00994 (413/41542). AF 95% confidence interval is 0.00915. There are 3 homozygotes in gnomad4. There are 280 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 569 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.-981T>C		5_prime_UTR_variant	1/19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.-981T>C		5_prime_UTR_variant	1/19	1	NM_015570.4	ENSP00000344087	P4
AUTS2	ENST00000644939.1	c.-981T>C		5_prime_UTR_variant	1/19			ENSP00000496726	A1

Frequencies

GnomAD3 genomes AF: 0.00372 AC: 565 AN: 152026 Hom.: 3 Cov.: 30

Gnomad AFR AF: 0.00987

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00433

GnomAD4 exome AF: 0.000134 AC: 1 AN: 7450 Hom.: 0 Cov.: 0 AF XY: 0.000187 AC XY: 1 AN XY: 5360

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00374 AC: 569 AN: 152136 Hom.: 3 Cov.: 30 AF XY: 0.00376 AC XY: 280 AN XY: 74374

Gnomad4 AFR AF: 0.00994

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.00428

Alfa AF: 0.00233 Hom.: 1

Bravo AF: 0.00419

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs535154040; hg19: chr7-69063659;