Genetic Variant AHI1:c.3485+38G>C (chr6-135300462-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001134831.2(AHI1):c.3485+38G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 1,536,176 control chromosomes in the GnomAD database, including 17,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 8009 hom., cov: 32)

Exomes 𝑓: 0.083 ( 9981 hom. )

Consequence

AHI1
NM_001134831.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.340

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=-0.81).

BP6

Variant 6-135300462-C-G is Benign according to our data. Variant chr6-135300462-C-G is described in ClinVar as [Benign]. Clinvar id is 260858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.3485+38G>C		intron_variant	Intron 27 of 28	ENST00000265602.11	NP_001128303.1	Q8N157-1Q8NER0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11 link	c.3485+38G>C		intron_variant	Intron 27 of 28	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33232

AN:

151778

Hom.:

7980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.0668

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.0684

Gnomad OTH

AF:

0.194

GnomAD3 exomes

AF:

0.104

AC:

19340

AN:

186302

Hom.:

2742

AF XY:

0.0961

AC XY:

9568

AN XY:

99514

show subpopulations

Gnomad AFR exome

AF:

0.613

Gnomad AMR exome

AF:

0.0905

Gnomad ASJ exome

AF:

0.0442

Gnomad EAS exome

AF:

0.0656

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.0679

Gnomad OTH exome

AF:

0.0795

GnomAD4 exome

AF:

0.0828

AC:

114573

AN:

1384282

Hom.:

9981

Cov.:

AF XY:

0.0815

AC XY:

55703

AN XY:

683338

show subpopulations

Gnomad4 AFR exome

AF:

0.626

Gnomad4 AMR exome

AF:

0.0972

Gnomad4 ASJ exome

AF:

0.0451

Gnomad4 EAS exome

AF:

0.0820

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0286

Gnomad4 NFE exome

AF:

0.0676

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.219

AC:

33321

AN:

151894

Hom.:

8009

Cov.:

AF XY:

0.212

AC XY:

15747

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0427

Gnomad4 EAS

AF:

0.0668

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.0684

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.116

Hom.:

546

Bravo

AF:

0.244

Asia WGS

AF:

0.167

AC:

580

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.6

DANN

Benign

0.64

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