Variant 6-135497759-C-A 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 ENST00000457866.6(AHI1):c.-293G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 199,288 control chromosomes in the GnomAD database, including 11,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7142 hom., cov: 33)

Exomes 𝑓: 0.40 ( 3920 hom. )

Consequence

AHI1
ENST00000457866.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.45

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:

AHI1-DT (HGNC:32526): (AHI1 divergent transcript)

AHI1-DT 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=-0.67).

BP6

Variant 6-135497759-C-A is Benign according to our data. Variant chr6-135497759-C-A is described in ClinVar as [Benign]. Clinvar id is 355518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-135497759-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2 linkuse as main transcript			upstream_gene_variant		ENST00000265602.11
AHI1-DT	NR_152842.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11 linkuse as main transcript			upstream_gene_variant		1	NM_001134831.2	P2	Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45583

AN:

152066

Hom.:

7135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.397

AC:

282

AN:

710

Hom.:

AF XY:

0.426

AC XY:

173

AN XY:

406

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.550

Gnomad NFE exome

AF:

0.412

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.399

AC:

18801

AN:

47106

Hom.:

3920

Cov.:

AF XY:

0.406

AC XY:

11816

AN XY:

29084

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.298

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.300

AC:

45615

AN:

152182

Hom.:

7142

Cov.:

AF XY:

0.299

AC XY:

22234

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.297

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.416

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.349

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.272

Hom.:

1262

Bravo

AF:

0.293

Asia WGS

AF:

0.317

AC:

1103

AN:

3476

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

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.81

Splicing

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