6-135284586-AAAAT-A

Variant names:

• chr6-135284586-AAAAT-A
• rs144339517
• NM_001134831.2:c.*1055_*1058delATTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001134831.2(AHI1):​c.*1055_*1058delATTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,078 control chromosomes in the GnomAD database, including 2,551 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (2551 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: AHI1 NM_001134831.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.603
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-135284586-AAAAT-A is Benign according to our data. Variant chr6-135284586-AAAAT-A is described in ClinVar as [Benign]. Clinvar id is 355484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.*1055_*1058delATTT		3_prime_UTR_variant	Exon 29 of 29	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.*1055_*1058delATTT		3_prime_UTR_variant	Exon 29 of 29	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15352 AN: 151960 Hom.: 2549 Cov.: 31

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00196

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.101 AC: 15388 AN: 152078 Hom.: 2551 Cov.: 31 AF XY: 0.0981 AC XY: 7294 AN XY: 74388

African (AFR) AF: 0.347 AC: 14333 AN: 41364

American (AMR) AF: 0.0431 AC: 660 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10586

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00196 AC: 133 AN: 68020

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0585 Hom.: 177

Bravo AF: 0.116

Asia WGS AF: 0.0230 AC: 80 AN: 3434

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Joubert syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60
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: rs144339517; hg19: chr6-135605724;