rs9321501

Positions:

• chr6-135320279-C-A
• chr6-135320279-C-G
• chr6-135320279-C-T

Variant summary

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

The NM_001134831.2(AHI1):​c.3329-1663G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,500 control chromosomes in the GnomAD database, including 22,325 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 0.54 (22325 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.3329-1663G>T		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.3329-1663G>T		intron_variant		1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82126 AN: 151386 Hom.: 22309 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.542 AC: 82184 AN: 151500 Hom.: 22325 Cov.: 31 AF XY: 0.548 AC XY: 40533 AN XY: 73976

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.559

Alfa AF: 0.544 Hom.: 3239

Bravo AF: 0.539

Asia WGS AF: 0.561 AC: 1949 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.5
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

Other links and lift over

dbSNP: rs9321501; hg19: chr6-135641417; COSMIC: COSV55624872;