rs17064526

Positions:

• chr6-135452087-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134831.2(AHI1):​c.1440+1254T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 152,226 control chromosomes in the GnomAD database, including 1,086 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 0.077 (1086 hom., cov: 32)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.1440+1254T>G		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.1440+1254T>G		intron_variant		1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11767 AN: 152108 Hom.: 1086 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0688

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0774 AC: 11787 AN: 152226 Hom.: 1086 Cov.: 32 AF XY: 0.0750 AC XY: 5586 AN XY: 74458

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0268 Hom.: 339

Bravo AF: 0.0879

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.66

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: rs17064526; hg19: chr6-135773225;