7-69598633-AGCGGCGGCG-AGCGGCG

Variant names:

• chr7-69598633-AGCG-A
• rs572172462
• NM_015570.4:c.-1003_-1001delGGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015570.4(AUTS2):​c.-1003_-1001delGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 148,204 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 30)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: AUTS2 NM_015570.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.013 (260/20066) while in subpopulation AFR AF= 0.0214 (3/140). AF 95% confidence interval is 0.0116. There are 0 homozygotes in gnomad4_exome. There are 166 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 260 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.-1003_-1001delGGC		5_prime_UTR_variant	Exon 1 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771	c.-1003_-1001delGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000644939	c.-1003_-1001delGGC		5_prime_UTR_variant	Exon 1 of 19			ENSP00000496726.1

Frequencies

GnomAD3 genomes AF: 0.0000156 AC: 2 AN: 128138 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000338

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0130 AC: 260 AN: 20066 Hom.: 0 AF XY: 0.0130 AC XY: 166 AN XY: 12770

Gnomad4 AFR exome AF: 0.0214

Gnomad4 AMR exome AF: 0.00735

Gnomad4 ASJ exome AF: 0.00420

Gnomad4 EAS exome AF: 0.0175

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.0000156 AC: 2 AN: 128138 Hom.: 0 Cov.: 30 AF XY: 0.0000319 AC XY: 2 AN XY: 62602

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000338

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs572172462; hg19: chr7-69063619;