rs2327612

Positions:

• chr6-135295481-A-C
• chr6-135295481-A-G

Variant summary

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

The NM_001134831.2(AHI1):​c.3486-4956T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,002 control chromosomes in the GnomAD database, including 8,116 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 0.20 (8116 hom., cov: 32)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3486-4956T>G		intron_variant		ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3486-4956T>G		intron_variant		1	NM_001134831.2	ENSP00000265602	P2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30655 AN: 151882 Hom.: 8083 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0948

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.202 AC: 30749 AN: 152002 Hom.: 8116 Cov.: 32 AF XY: 0.196 AC XY: 14551 AN XY: 74334

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.0946

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.0874

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.176

Alfa AF: 0.132 Hom.: 574

Bravo AF: 0.226

Asia WGS AF: 0.109 AC: 381 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	0.11
DANN	Benign	0.33

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: rs2327612; hg19: chr6-135616619;