chr6-135442447-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001134831.2(AHI1):​c.1912+135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 960,342 control chromosomes in the GnomAD database, including 465,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.99 ( 74315 hom., cov: 33)
Exomes 𝑓: 0.98 ( 391035 hom. )

Consequence

AHI1
NM_001134831.2 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.706

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • Joubert syndrome 3
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Ambry Genetics
  • Joubert syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Joubert syndrome with ocular defect
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • retinitis pigmentosa
    Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 6-135442447-T-C is Benign according to our data. Variant chr6-135442447-T-C is described in ClinVar as Benign. ClinVar VariationId is 1246420.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AHI1NM_001134831.2 linkc.1912+135A>G intron_variant Intron 14 of 28 ENST00000265602.11 NP_001128303.1 Q8N157-1Q8NER0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AHI1ENST00000265602.11 linkc.1912+135A>G intron_variant Intron 14 of 28 1 NM_001134831.2 ENSP00000265602.6 Q8N157-1

Frequencies

GnomAD3 genomes
AF:
0.988
AC:
150336
AN:
152208
Hom.:
74257
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.995
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.994
Gnomad ASJ
AF:
0.992
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.994
Gnomad FIN
AF:
0.988
Gnomad MID
AF:
0.991
Gnomad NFE
AF:
0.980
Gnomad OTH
AF:
0.989
GnomAD4 exome
AF:
0.984
AC:
794909
AN:
808016
Hom.:
391035
AF XY:
0.984
AC XY:
387075
AN XY:
393452
show subpopulations
African (AFR)
AF:
0.997
AC:
17867
AN:
17912
American (AMR)
AF:
0.993
AC:
11799
AN:
11882
Ashkenazi Jewish (ASJ)
AF:
0.990
AC:
13696
AN:
13828
East Asian (EAS)
AF:
1.00
AC:
28894
AN:
28894
South Asian (SAS)
AF:
0.994
AC:
21564
AN:
21700
European-Finnish (FIN)
AF:
0.984
AC:
35661
AN:
36224
Middle Eastern (MID)
AF:
0.991
AC:
2744
AN:
2770
European-Non Finnish (NFE)
AF:
0.982
AC:
627519
AN:
639182
Other (OTH)
AF:
0.987
AC:
35165
AN:
35624
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
619
1238
1858
2477
3096
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
12412
24824
37236
49648
62060
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.988
AC:
150453
AN:
152326
Hom.:
74315
Cov.:
33
AF XY:
0.988
AC XY:
73596
AN XY:
74484
show subpopulations
African (AFR)
AF:
0.995
AC:
41368
AN:
41574
American (AMR)
AF:
0.994
AC:
15207
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.992
AC:
3443
AN:
3470
East Asian (EAS)
AF:
1.00
AC:
5186
AN:
5188
South Asian (SAS)
AF:
0.994
AC:
4802
AN:
4830
European-Finnish (FIN)
AF:
0.988
AC:
10490
AN:
10620
Middle Eastern (MID)
AF:
0.990
AC:
291
AN:
294
European-Non Finnish (NFE)
AF:
0.980
AC:
66663
AN:
68024
Other (OTH)
AF:
0.989
AC:
2091
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
96
192
287
383
479
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
916
1832
2748
3664
4580
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.974
Hom.:
3894
Bravo
AF:
0.989
Asia WGS
AF:
0.997
AC:
3466
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

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
-0.90
CADD
Benign
0.72
DANN
Benign
0.60
PhyloP100
-0.71
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2614274; hg19: chr6-135763585; API