6-135327875-C-T

Variant names:

• chr6-135327875-C-T
• rs7772681
• NM_001134831.2:c.3166-4551G>A

Variant summary

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

The NM_001134831.2(AHI1):​c.3166-4551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,062 control chromosomes in the GnomAD database, including 17,468 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 0.46 (17468 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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]

ENSG00000287094 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3166-4551G>A		intron_variant	Intron 24 of 28	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3166-4551G>A		intron_variant	Intron 24 of 28	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69545 AN: 151946 Hom.: 17469 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.457 AC: 69553 AN: 152062 Hom.: 17468 Cov.: 31 AF XY: 0.464 AC XY: 34506 AN XY: 74348

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.477

Alfa AF: 0.513 Hom.: 9245

Bravo AF: 0.445

Asia WGS AF: 0.503 AC: 1748 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.29

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: rs7772681; hg19: chr6-135649013; COSMIC: COSV55624921; COSMIC: COSV55624921;