rs9483826

Variant names:

• chr6-135298378-G-A
• rs9483826
• NM_001134831.2:c.3485+2122C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-135298378-G-A
• chr6-135298378-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134831.2(AHI1):​c.3485+2122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 149,420 control chromosomes in the GnomAD database, including 9,865 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 0.22 (9865 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 3 publications found

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]

AHI1 Gene-Disease associations (from GenCC):

• Joubert syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ENSG00000234084 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3485+2122C>T		intron_variant	Intron 27 of 28	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3485+2122C>T		intron_variant	Intron 27 of 28	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33352 AN: 149342 Hom.: 9831 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0405

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.224 AC: 33446 AN: 149420 Hom.: 9865 Cov.: 31 AF XY: 0.217 AC XY: 15795 AN XY: 72750

African (AFR) AF: 0.680 AC: 27960 AN: 41116

American (AMR) AF: 0.103 AC: 1542 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.0405 AC: 140 AN: 3456

East Asian (EAS) AF: 0.0158 AC: 81 AN: 5128

South Asian (SAS) AF: 0.0878 AC: 417 AN: 4750

European-Finnish (FIN) AF: 0.0166 AC: 153 AN: 9240

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.0403 AC: 2717 AN: 67426

Other (OTH) AF: 0.192 AC: 398 AN: 2076

Alfa AF: 0.200 Hom.: 878

Bravo AF: 0.247

Asia WGS AF: 0.113 AC: 394 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	0.097
DANN	Benign	0.26
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9483826; hg19: chr6-135619516;