rs41288017

Positions:

chr6-135428747-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001134831.2(AHI1):c.2505G>A(p.Arg835Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,602,692 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 26 hom. )

Consequence

AHI1
NM_001134831.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.54

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 (HGNC:):

AHI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 6-135428747-C-T is Benign according to our data. Variant chr6-135428747-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 194870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-135428747-C-T is described in Lovd as [Benign]. Variant chr6-135428747-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.54 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2 linkuse as main transcript	c.2505G>A	p.Arg835Arg	synonymous_variant	19/29	ENST00000265602.11	NP_001128303.1	Q8N157-1Q8NER0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11 linkuse as main transcript	c.2505G>A	p.Arg835Arg	synonymous_variant	19/29	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.00379

AC:

575

AN:

151726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00526

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00623

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00385

AC:

907

AN:

235472

Hom.:

AF XY:

0.00405

AC XY:

516

AN XY:

127380

show subpopulations

Gnomad AFR exome

AF:

0.000753

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.00155

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.00633

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00481

AC:

6977

AN:

1450848

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

3532

AN XY:

720906

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00504

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00164

Gnomad4 FIN exome

AF:

0.000303

Gnomad4 NFE exome

AF:

0.00562

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.00379

AC:

575

AN:

151844

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

273

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00525

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00622

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00495

Hom.:

Bravo

AF:

0.00420

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	AHI1: BP4, BP7, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 18782849, 16453322) -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 05, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Joubert syndrome 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Familial aplasia of the vermis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

7.5

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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