rs11970282

chr6-135285753-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001134831.2(AHI1):c.3589-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 945,872 control chromosomes in the GnomAD database, including 3,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1588 hom., cov: 33)
  • Exomes 𝑓: 0.065 (2338 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.41

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 6-135285753-T-C is Benign according to our data. Variant chr6-135285753-T-C is described in ClinVar as [Benign]. Clinvar id is 675064.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.3589-106A>G		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.3589-106A>G		intron_variant		1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17656 AN: 152160 Hom.: 1577 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0648 AC: 51441 AN: 793594 Hom.: 2338 AF XY: 0.0654 AC XY: 27015 AN XY: 413026

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.0673

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.0813

Gnomad4 SAS exome AF: 0.0931

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.0580

Gnomad4 OTH exome AF: 0.0725

GnomAD4 genome AF: 0.116 AC: 17707 AN: 152278 Hom.: 1588 Cov.: 33 AF XY: 0.112 AC XY: 8343 AN XY: 74482

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0840

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0675

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.110

Alfa AF: 0.113 Hom.: 223

Bravo AF: 0.125

Asia WGS AF: 0.144 AC: 502 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.15
Dann	Benign	0.72

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: rs11970282; hg19: chr6-135606891;