Variant chr6-135497680-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001134831.2(AHI1):c.-299G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 163,520 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 146 hom., cov: 33)

Exomes 𝑓: 0.036 ( 10 hom. )

Consequence

AHI1
NM_001134831.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.881

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=-0.72).

BP6

Variant 6-135497680-C-T is Benign according to our data. Variant chr6-135497680-C-T is described in ClinVar as [Benign]. Clinvar id is 355514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0349 (5316/152366) while in subpopulation AMR AF= 0.0479 (733/15310). AF 95% confidence interval is 0.045. There are 146 homozygotes in gnomad4. There are 2627 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 146 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2 linkuse as main transcript	c.-299G>A		5_prime_UTR_variant	1/29	ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11 linkuse as main transcript	c.-299G>A		5_prime_UTR_variant	1/29	1	NM_001134831.2	P2	Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5317

AN:

152250

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00902

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0479

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0277

Gnomad FIN

AF:

0.0716

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0463

Gnomad OTH

AF:

0.0287

GnomAD4 exome

AF:

0.0359

AC:

400

AN:

11154

Hom.:

Cov.:

AF XY:

0.0354

AC XY:

251

AN XY:

7084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0291

Gnomad4 FIN exome

AF:

0.0476

Gnomad4 NFE exome

AF:

0.0411

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0349

AC:

5316

AN:

152366

Hom.:

146

Cov.:

AF XY:

0.0353

AC XY:

2627

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00899

Gnomad4 AMR

AF:

0.0479

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0277

Gnomad4 FIN

AF:

0.0716

Gnomad4 NFE

AF:

0.0463

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0405

Hom.:

Bravo

AF:

0.0339

Asia WGS

AF:

0.0140

AC:

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

Dec 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.3

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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