6-135427062-A-G

Position:

• chr6-135427062-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001134831.2(AHI1):​c.2764+105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 1,153,620 control chromosomes in the GnomAD database, including 498,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.88 (59966 hom., cov: 32)
  • Exomes 𝑓: 0.94 (438990 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00200

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-135427062-A-G is Benign according to our data. Variant chr6-135427062-A-G is described in ClinVar as [Benign]. Clinvar id is 1247098.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.2764+105T>C		intron_variant		ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.2764+105T>C		intron_variant		1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134094 AN: 151514 Hom.: 59938 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.898

GnomAD4 exome AF: 0.935 AC: 937264 AN: 1001988 Hom.: 438990 AF XY: 0.937 AC XY: 474771 AN XY: 506816

Gnomad4 AFR exome AF: 0.744

Gnomad4 AMR exome AF: 0.931

Gnomad4 ASJ exome AF: 0.978

Gnomad4 EAS exome AF: 0.968

Gnomad4 SAS exome AF: 0.949

Gnomad4 FIN exome AF: 0.970

Gnomad4 NFE exome AF: 0.936

Gnomad4 OTH exome AF: 0.930

GnomAD4 genome AF: 0.885 AC: 134176 AN: 151632 Hom.: 59966 Cov.: 32 AF XY: 0.888 AC XY: 65889 AN XY: 74172

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.935

Gnomad4 OTH AF: 0.897

Alfa AF: 0.899 Hom.: 13684

Bravo AF: 0.876

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs2757639; hg19: chr6-135748200;