6-135433333-C-T

Position:

• chr6-135433333-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001134831.2(AHI1):​c.2037-77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,010,896 control chromosomes in the GnomAD database, including 424,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (54373 hom., cov: 32)
  • Exomes 𝑓: 0.93 (369754 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.174

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]

AHI1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 6-135433333-C-T is Benign according to our data. Variant chr6-135433333-C-T is described in ClinVar as [Benign]. Clinvar id is 1188864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.2037-77G>A		intron_variant		ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.2037-77G>A		intron_variant		1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125886 AN: 152020 Hom.: 54354 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.843

GnomAD4 exome AF: 0.926 AC: 794955 AN: 858758 Hom.: 369754 AF XY: 0.928 AC XY: 406686 AN XY: 438310

Gnomad4 AFR exome AF: 0.547

Gnomad4 AMR exome AF: 0.910

Gnomad4 ASJ exome AF: 0.955

Gnomad4 EAS exome AF: 0.966

Gnomad4 SAS exome AF: 0.949

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.932

Gnomad4 OTH exome AF: 0.908

GnomAD4 genome AF: 0.828 AC: 125955 AN: 152138 Hom.: 54373 Cov.: 32 AF XY: 0.834 AC XY: 62041 AN XY: 74404

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.890

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.842

Alfa AF: 0.896 Hom.: 24830

Bravo AF: 0.811

Asia WGS AF: 0.903 AC: 3135 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Joubert syndrome 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.071
DANN	Benign	0.17

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: rs737561; hg19: chr6-135754471;