rs7759971

Positions:

• chr6-135425746-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.2764+1421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,528 control chromosomes in the GnomAD database, including 7,174 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 0.30 (7174 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.2764+1421G>A		intron_variant		ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.2764+1421G>A		intron_variant		1	NM_001134831.2	ENSP00000265602	P2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44850 AN: 151410 Hom.: 7171 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.296 AC: 44859 AN: 151528 Hom.: 7174 Cov.: 31 AF XY: 0.295 AC XY: 21856 AN XY: 74116

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.313

Alfa AF: 0.316 Hom.: 1126

Bravo AF: 0.289

Asia WGS AF: 0.316 AC: 1097 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.38

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: rs7759971; hg19: chr6-135746884;