Variant 6-135492113-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001134831.2(AHI1):c.10+115C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 664,456 control chromosomes in the GnomAD database, including 257,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 47816 hom., cov: 32)

Exomes 𝑓: 0.90 ( 209379 hom. )

Consequence

AHI1
NM_001134831.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.662

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-135492113-G-T is Benign according to our data. Variant chr6-135492113-G-T is described in ClinVar as [Benign]. Clinvar id is 673960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2 linkuse as main transcript	c.10+115C>A		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11 linkuse as main transcript	c.10+115C>A		intron_variant		1	NM_001134831.2	P2	Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113609

AN:

151990

Hom.:

47815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.966

Gnomad AMR

AF:

0.850

Gnomad ASJ

AF:

0.940

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.914

Gnomad FIN

AF:

0.956

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.914

Gnomad OTH

AF:

0.772

GnomAD4 exome

AF:

0.899

AC:

460469

AN:

512350

Hom.:

209379

AF XY:

0.901

AC XY:

235491

AN XY:

261318

show subpopulations

Gnomad4 AFR exome

AF:

0.314

Gnomad4 AMR exome

AF:

0.870

Gnomad4 ASJ exome

AF:

0.936

Gnomad4 EAS exome

AF:

0.922

Gnomad4 SAS exome

AF:

0.908

Gnomad4 FIN exome

AF:

0.951

Gnomad4 NFE exome

AF:

0.914

Gnomad4 OTH exome

AF:

0.861

GnomAD4 genome

AF:

0.747

AC:

113639

AN:

152106

Hom.:

47816

Cov.:

AF XY:

0.756

AC XY:

56204

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.320

Gnomad4 AMR

AF:

0.850

Gnomad4 ASJ

AF:

0.940

Gnomad4 EAS

AF:

0.905

Gnomad4 SAS

AF:

0.914

Gnomad4 FIN

AF:

0.956

Gnomad4 NFE

AF:

0.914

Gnomad4 OTH

AF:

0.769

Alfa

AF:

0.820

Hom.:

6804

Bravo

AF:

0.719

Asia WGS

AF:

0.827

AC:

2868

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 14, 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

-0.85

CADD

Benign

4.4

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over