Variant rs780835322 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000265602.11(AHI1):c.2961+6_2961+7insGAC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.012 in 1,611,070 control chromosomes in the GnomAD database, including 139 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

AHI1
ENST00000265602.11 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.79

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 -10 ACMG points.

BP6

Variant 6-135411341-A-AGTC is Benign according to our data. Variant chr6-135411341-A-AGTC is described in ClinVar as [Benign]. Clinvar id is 220132.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0123 (17879/1458706) while in subpopulation MID AF= 0.0222 (128/5764). AF 95% confidence interval is 0.0191. There are 130 homozygotes in gnomad4_exome. There are 8914 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2 linkuse as main transcript	c.2961+6_2961+7insGAC		splice_region_variant, 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.2961+6_2961+7insGAC		splice_region_variant, intron_variant		1	NM_001134831.2	ENSP00000265602	P2	Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1489

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00791

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.0110

AC:

2725

AN:

248044

Hom.:

AF XY:

0.0110

AC XY:

1483

AN XY:

134544

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.00815

Gnomad ASJ exome

AF:

0.00979

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0123

AC:

17879

AN:

1458706

Hom.:

130

Cov.:

AF XY:

0.0123

AC XY:

8914

AN XY:

725680

show subpopulations

Gnomad4 AFR exome

AF:

0.00189

Gnomad4 AMR exome

AF:

0.00863

Gnomad4 ASJ exome

AF:

0.00947

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.00986

GnomAD4 genome

AF:

0.00976

AC:

1487

AN:

152364

Hom.:

Cov.:

AF XY:

0.00992

AC XY:

739

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00240

Gnomad4 AMR

AF:

0.00790

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0140

Hom.:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2019

This variant is associated with the following publications: (PMID: 31054281) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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