rs9321501

Variant names:

• chr6-135320279-C-A
• rs9321501
• NM_001134831.2:c.3329-1663G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134831.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	NM_001134831.2	MANE Select	c.3329-1663G>T		intron	N/A	NP_001128303.1
	AHI1	NM_001134830.2		c.3329-1663G>T		intron	N/A	NP_001128302.1
	AHI1	NM_001350503.2		c.3329-1663G>T		intron	N/A	NP_001337432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	ENST00000265602.11	TSL:1 MANE Select	c.3329-1663G>T		intron	N/A	ENSP00000265602.6
	AHI1	ENST00000367800.8	TSL:1	c.3329-1663G>T		intron	N/A	ENSP00000356774.4
	AHI1	ENST00000457866.6	TSL:1	c.3329-1663G>T		intron	N/A	ENSP00000388650.2

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

African (AFR) AF: 0.473 AC: 19517 AN: 41228

American (AMR) AF: 0.588 AC: 8968 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2096 AN: 3468

East Asian (EAS) AF: 0.623 AC: 3202 AN: 5142

South Asian (SAS) AF: 0.525 AC: 2523 AN: 4804

European-Finnish (FIN) AF: 0.624 AC: 6495 AN: 10416

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37408 AN: 67884

Other (OTH) AF: 0.559 AC: 1179 AN: 2110

Alfa AF: 0.542 Hom.: 3332

Bravo AF: 0.539

Asia WGS AF: 0.561 AC: 1949 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.5
DANN	Benign	0.81
PhyloP100		-0.40
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: rs9321501; hg19: chr6-135641417; COSMIC: COSV55624872;