Genetic Variant AHI1:c.-55+449A>G (chr6-135495365-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134831.2(AHI1):c.-55+449A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,200 control chromosomes in the GnomAD database, including 48,071 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 48057 hom., cov: 31)

Exomes 𝑓: 0.97 ( 14 hom. )

Consequence

AHI1
NM_001134831.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.375

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.-55+449A>G		intron_variant	Intron 3 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.-55+449A>G		intron_variant	Intron 3 of 28	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

114040

AN:

152054

Hom.:

48057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.966

Gnomad AMR

AF:

0.852

Gnomad ASJ

AF:

0.941

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.915

Gnomad FIN

AF:

0.956

Gnomad MID

AF:

0.879

Gnomad NFE

AF:

0.916

Gnomad OTH

AF:

0.774

GnomAD4 exome

AF:

0.967

AC:

AN:

Hom.:

Cov.:

AF XY:

0.964

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.750

AC:

114071

AN:

152170

Hom.:

48057

Cov.:

AF XY:

0.758

AC XY:

56399

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.325

Gnomad4 AMR

AF:

0.852

Gnomad4 ASJ

AF:

0.941

Gnomad4 EAS

AF:

0.905

Gnomad4 SAS

AF:

0.914

Gnomad4 FIN

AF:

0.956

Gnomad4 NFE

AF:

0.916

Gnomad4 OTH

AF:

0.770

Alfa

AF:

0.743

Hom.:

7220

Bravo

AF:

0.722

Asia WGS

AF:

0.829

AC:

2883

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.3

DANN

Benign

0.81

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over