chr6-135496997-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001134831.2(AHI1):​c.-140+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,264 control chromosomes in the GnomAD database, including 55,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.84 ( 55907 hom., cov: 32)

Consequence

AHI1
NM_001134831.2 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.927
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 6-135496997-C-T is Benign according to our data. Variant chr6-135496997-C-T is described in ClinVar as [Benign]. Clinvar id is 1267699.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AHI1NM_001134831.2 linkuse as main transcriptc.-140+191G>A intron_variant ENST00000265602.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AHI1ENST00000265602.11 linkuse as main transcriptc.-140+191G>A intron_variant 1 NM_001134831.2 P2Q8N157-1

Frequencies

GnomAD3 genomes
AF:
0.845
AC:
128554
AN:
152146
Hom.:
55895
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.611
Gnomad AMI
AF:
0.967
Gnomad AMR
AF:
0.894
Gnomad ASJ
AF:
0.956
Gnomad EAS
AF:
0.958
Gnomad SAS
AF:
0.949
Gnomad FIN
AF:
0.976
Gnomad MID
AF:
0.896
Gnomad NFE
AF:
0.932
Gnomad OTH
AF:
0.852
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.845
AC:
128613
AN:
152264
Hom.:
55907
Cov.:
32
AF XY:
0.850
AC XY:
63308
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.611
Gnomad4 AMR
AF:
0.894
Gnomad4 ASJ
AF:
0.956
Gnomad4 EAS
AF:
0.958
Gnomad4 SAS
AF:
0.948
Gnomad4 FIN
AF:
0.976
Gnomad4 NFE
AF:
0.932
Gnomad4 OTH
AF:
0.852
Alfa
AF:
0.853
Hom.:
8081
Bravo
AF:
0.829
Asia WGS
AF:
0.903
AC:
3137
AN:
3472

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 submitterclinical testingGeneDxJan 28, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
2.7
DANN
Benign
0.90

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.

Other links and lift over

dbSNP: rs6928455; hg19: chr6-135818135; API