rs2207000

chr6-135302695-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001134831.2(AHI1):c.3427-2137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,215,734 control chromosomes in the GnomAD database, including 29,017 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 0.27 (7052 hom., cov: 32)
  • Exomes 𝑓: 0.20 (21965 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.3427-2137G>A		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.3427-2137G>A		intron_variant		1	NM_001134831.2	P2
	ENST00000444302.1	n.123+1005C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41164 AN: 151930 Hom.: 7027 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.197 AC: 209058 AN: 1063686 Hom.: 21965 Cov.: 34 AF XY: 0.195 AC XY: 100709 AN XY: 517426

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.271 AC: 41238 AN: 152048 Hom.: 7052 Cov.: 32 AF XY: 0.265 AC XY: 19702 AN XY: 74330

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.277

Alfa AF: 0.209 Hom.: 4851

Bravo AF: 0.281

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	11
Dann	Benign	0.68

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: rs2207000; hg19: chr6-135623833;