Variant chr6-135455977-G-A 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 ENST00000265602.11(AHI1):c.1152-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,264,824 control chromosomes in the GnomAD database, including 470 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: 0.027 ( 431 hom. )

Consequence

AHI1
ENST00000265602.11 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.536

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=-0.86).

BP6

Variant 6-135455977-G-A is Benign according to our data. Variant chr6-135455977-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 675181.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 = 0.0204 (3107/152134) while in subpopulation SAS AF= 0.0388 (187/4816). AF 95% confidence interval is 0.0343. There are 39 homozygotes in gnomad4. There are 1494 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.1152-51C>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.1152-51C>T		intron_variant		1	NM_001134831.2	ENSP00000265602	P2	Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3106

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00563

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0335

Gnomad SAS

AF:

0.0382

Gnomad FIN

AF:

0.00813

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0245

GnomAD4 exome

AF:

0.0270

AC:

30098

AN:

1112690

Hom.:

431

AF XY:

0.0269

AC XY:

14414

AN XY:

534886

show subpopulations

Gnomad4 AFR exome

AF:

0.00434

Gnomad4 AMR exome

AF:

0.0383

Gnomad4 ASJ exome

AF:

0.00285

Gnomad4 EAS exome

AF:

0.0337

Gnomad4 SAS exome

AF:

0.0314

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.0284

Gnomad4 OTH exome

AF:

0.0263

GnomAD4 genome

AF:

0.0204

AC:

3107

AN:

152134

Hom.:

Cov.:

AF XY:

0.0201

AC XY:

1494

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00559

Gnomad4 AMR

AF:

0.0329

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0334

Gnomad4 SAS

AF:

0.0388

Gnomad4 FIN

AF:

0.00813

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0262

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.0570

AC:

198

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

DANN

Benign

0.67

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