rs1535436

chr6-135452010-G-Achr6-135452010-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001134831.2(AHI1):c.1440+1331C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 152,226 control chromosomes in the GnomAD database, including 53 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 0.024 (53 hom., cov: 32)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0242 (3677/152226) while in subpopulation AMR AF= 0.0381 (582/15290). AF 95% confidence interval is 0.0355. There are 53 homozygotes in gnomad4. There are 1788 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.1440+1331C>T		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.1440+1331C>T		intron_variant		1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3677 AN: 152108 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0242 AC: 3677 AN: 152226 Hom.: 53 Cov.: 32 AF XY: 0.0240 AC XY: 1788 AN XY: 74418

Gnomad4 AFR AF: 0.00612

Gnomad4 AMR AF: 0.0381

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0244 Hom.: 37

Bravo AF: 0.0239

Asia WGS AF: 0.00808 AC: 28 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	0.48
Dann	Benign	0.45

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: rs1535436; hg19: chr6-135773148;