6-135386128-A-T

Position:

• chr6-135386128-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134831.2(AHI1):​c.3109+8648T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 152,266 control chromosomes in the GnomAD database, including 69,879 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 0.96 (69879 hom., cov: 30)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.3109+8648T>A		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.3109+8648T>A		intron_variant		1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145715 AN: 152148 Hom.: 69821 Cov.: 30

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.958 AC: 145833 AN: 152266 Hom.: 69879 Cov.: 30 AF XY: 0.959 AC XY: 71402 AN XY: 74440

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.978

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.957

Alfa AF: 0.939 Hom.: 3131

Bravo AF: 0.960

Asia WGS AF: 0.990 AC: 3445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.42

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: rs6570004; hg19: chr6-135707266; COSMIC: COSV55625146; COSMIC: COSV55625146;