6-135285247-C-CCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001134831.2(AHI1):c.*397_*398insTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 233,098 control chromosomes in the GnomAD database, including 1,712 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1578 hom., cov: 31)
  • Exomes 𝑓: 0.051 (134 hom.)
• Consequence: AHI1 NM_001134831.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.592

Genes affected

AHI1 (HGNC:21575): (Abelson helper integration site 1) This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-135285247-C-CCA is Benign according to our data. Variant chr6-135285247-C-CCA is described in ClinVar as [Likely_benign]. Clinvar id is 355489.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.*397_*398insTG		3_prime_UTR_variant	29/29	ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.*397_*398insTG		3_prime_UTR_variant	29/29	1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17642 AN: 152092 Hom.: 1567 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0507 AC: 4102 AN: 80888 Hom.: 134 Cov.: 0 AF XY: 0.0513 AC XY: 2172 AN XY: 42334

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0646

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.0472

Gnomad4 SAS exome AF: 0.0678

Gnomad4 FIN exome AF: 0.0207

Gnomad4 NFE exome AF: 0.0459

Gnomad4 OTH exome AF: 0.0498

GnomAD4 genome AF: 0.116 AC: 17693 AN: 152210 Hom.: 1578 Cov.: 31 AF XY: 0.112 AC XY: 8322 AN XY: 74420

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0923 Hom.: 107

Bravo AF: 0.125

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial aplasia of the vermis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs397885237; hg19: chr6-135606385;