6-135394237-C-T

Position:

• chr6-135394237-C-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+539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 151,848 control chromosomes in the GnomAD database, including 26,951 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 0.59 (26951 hom., cov: 32)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3109+539G>A		intron_variant		ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3109+539G>A		intron_variant		1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90170 AN: 151730 Hom.: 26932 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.594 AC: 90243 AN: 151848 Hom.: 26951 Cov.: 32 AF XY: 0.596 AC XY: 44215 AN XY: 74204

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.606

Alfa AF: 0.565 Hom.: 7630

Bravo AF: 0.601

Asia WGS AF: 0.589 AC: 2042 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.43
DANN	Benign	0.49

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: rs2614265; hg19: chr6-135715375;