Variant chr6-135285617-C-G 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.*28G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,602,404 control chromosomes in the GnomAD database, including 6,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1583 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4640 hom. )

Consequence

AHI1
NM_001134831.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.575

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=-0.88).

BP6

Variant 6-135285617-C-G is Benign according to our data. Variant chr6-135285617-C-G is described in ClinVar as [Benign]. Clinvar id is 260835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-135285617-C-G is described in Lovd as [Benign].

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	Protein	UniProt
AHI1	NM_001134831.2 linkuse as main transcript	c.*28G>C		3_prime_UTR_variant	29/29	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11 linkuse as main transcript	c.*28G>C		3_prime_UTR_variant	29/29	1	NM_001134831.2	ENSP00000265602	P2	Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17652

AN:

152076

Hom.:

1572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.0844

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.0673

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0666

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.0730

AC:

17639

AN:

241654

Hom.:

994

AF XY:

0.0711

AC XY:

9319

AN XY:

131110

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.0688

Gnomad ASJ exome

AF:

0.0268

Gnomad EAS exome

AF:

0.0610

Gnomad SAS exome

AF:

0.0955

Gnomad FIN exome

AF:

0.0250

Gnomad NFE exome

AF:

0.0614

Gnomad OTH exome

AF:

0.0622

GnomAD4 exome

AF:

0.0708

AC:

102717

AN:

1450210

Hom.:

4640

Cov.:

AF XY:

0.0707

AC XY:

51028

AN XY:

721362

show subpopulations

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.0715

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.0807

Gnomad4 SAS exome

AF:

0.0986

Gnomad4 FIN exome

AF:

0.0281

Gnomad4 NFE exome

AF:

0.0654

Gnomad4 OTH exome

AF:

0.0775

GnomAD4 genome

AF:

0.116

AC:

17703

AN:

152194

Hom.:

1583

Cov.:

AF XY:

0.112

AC XY:

8331

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.0841

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.0673

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.0666

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0385

Hom.:

Bravo

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.8

DANN

Benign

0.59

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