rs2614264

Positions:

• chr6-135389556-G-A
• chr6-135389556-G-C

Variant summary

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

The NM_001134831.2(AHI1):​c.3109+5220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,932 control chromosomes in the GnomAD database, including 24,017 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 0.56 (24017 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3109+5220C>T		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+5220C>T		intron_variant		1	NM_001134831.2	ENSP00000265602	P2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85260 AN: 151814 Hom.: 24007 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.562 AC: 85312 AN: 151932 Hom.: 24017 Cov.: 31 AF XY: 0.565 AC XY: 41936 AN XY: 74256

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.575

Alfa AF: 0.495 Hom.: 2132

Bravo AF: 0.563

Asia WGS AF: 0.568 AC: 1973 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.2
DANN	Benign	0.75

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: rs2614264; hg19: chr6-135710694; COSMIC: COSV55625189;