rs11970282

Variant names:

• chr6-135285753-T-C
• rs11970282
• NM_001134831.2:c.3589-106A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001134831.2(AHI1):​c.3589-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 945,872 control chromosomes in the GnomAD database, including 3,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1588 hom., cov: 33)
  • Exomes 𝑓: 0.065 (2338 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.41
• Publications: 1 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, Laboratory for Molecular Medicine, ClinGen, 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 6-135285753-T-C is Benign according to our data. Variant chr6-135285753-T-C is described in ClinVar as Benign. ClinVar VariationId is 675064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	NM_001134831.2	MANE Select	c.3589-106A>G		intron	N/A	NP_001128303.1	Q8N157-1
	AHI1	NM_001134830.2		c.3589-106A>G		intron	N/A	NP_001128302.1	Q8N157-1
	AHI1	NM_001350503.2		c.3589-106A>G		intron	N/A	NP_001337432.1	Q8N157-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	ENST00000265602.11	TSL:1 MANE Select	c.3589-106A>G		intron	N/A	ENSP00000265602.6	Q8N157-1
	AHI1	ENST00000367800.8	TSL:1	c.3589-106A>G		intron	N/A	ENSP00000356774.4	Q8N157-1
	AHI1	ENST00000457866.6	TSL:1	c.3589-106A>G		intron	N/A	ENSP00000388650.2	Q8N157-1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17656 AN: 152160 Hom.: 1577 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0648 AC: 51441 AN: 793594 Hom.: 2338 AF XY: 0.0654 AC XY: 27015 AN XY: 413026

African (AFR) AF: 0.235 AC: 4441 AN: 18860

American (AMR) AF: 0.0673 AC: 2131 AN: 31648

Ashkenazi Jewish (ASJ) AF: 0.0263 AC: 547 AN: 20810

East Asian (EAS) AF: 0.0813 AC: 2714 AN: 33388

South Asian (SAS) AF: 0.0931 AC: 5941 AN: 63798

European-Finnish (FIN) AF: 0.0282 AC: 1116 AN: 39560

Middle Eastern (MID) AF: 0.0644 AC: 261 AN: 4054

European-Non Finnish (NFE) AF: 0.0580 AC: 31513 AN: 543198

Other (OTH) AF: 0.0725 AC: 2777 AN: 38278

GnomAD4 genome AF: 0.116 AC: 17707 AN: 152278 Hom.: 1588 Cov.: 33 AF XY: 0.112 AC XY: 8343 AN XY: 74482

African (AFR) AF: 0.250 AC: 10385 AN: 41532

American (AMR) AF: 0.0840 AC: 1286 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.0675 AC: 350 AN: 5186

South Asian (SAS) AF: 0.108 AC: 522 AN: 4832

European-Finnish (FIN) AF: 0.0243 AC: 258 AN: 10622

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4523 AN: 68014

Other (OTH) AF: 0.110 AC: 232 AN: 2112

Alfa AF: 0.118 Hom.: 258

Bravo AF: 0.125

Asia WGS AF: 0.144 AC: 502 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.72
PhyloP100		-2.4
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: rs11970282; hg19: chr6-135606891;