Variant rs17053651 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.1780-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,512,530 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 39 hom., cov: 32)

Exomes 𝑓: 0.028 ( 582 hom. )

Consequence

AHI1
NM_001134831.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.394

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-135442761-G-A is Benign according to our data. Variant chr6-135442761-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0203 (3096/152212) while in subpopulation SAS AF= 0.0378 (182/4818). AF 95% confidence interval is 0.0333. There are 39 homozygotes in gnomad4. There are 1487 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2 linkuse as main transcript	c.1780-47C>T		intron_variant		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.1780-47C>T		intron_variant		1	NM_001134831.2	ENSP00000265602	P2	Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3094

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00536

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.00812

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0281

AC:

5244

AN:

186644

Hom.:

AF XY:

0.0287

AC XY:

2909

AN XY:

101354

show subpopulations

Gnomad AFR exome

AF:

0.00629

Gnomad AMR exome

AF:

0.0438

Gnomad ASJ exome

AF:

0.00330

Gnomad EAS exome

AF:

0.0308

Gnomad SAS exome

AF:

0.0366

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.0303

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0279

AC:

37932

AN:

1360318

Hom.:

582

Cov.:

AF XY:

0.0279

AC XY:

18718

AN XY:

671712

show subpopulations

Gnomad4 AFR exome

AF:

0.00431

Gnomad4 AMR exome

AF:

0.0419

Gnomad4 ASJ exome

AF:

0.00301

Gnomad4 EAS exome

AF:

0.0343

Gnomad4 SAS exome

AF:

0.0348

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.0289

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0203

AC:

3096

AN:

152212

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1487

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00534

Gnomad4 AMR

AF:

0.0329

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0335

Gnomad4 SAS

AF:

0.0378

Gnomad4 FIN

AF:

0.00812

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0215

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.66

DANN

Benign

0.75

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