rs7756167

Positions:

• chr6-135301867-A-G

Variant summary

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

The ENST00000265602.11(AHI1):​c.3427-1309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 985,342 control chromosomes in the GnomAD database, including 16,306 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 0.24 (9963 hom., cov: 33)
  • Exomes 𝑓: 0.083 (6343 hom.)
• Consequence: AHI1 ENST00000265602.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3427-1309T>C		intron_variant		ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3427-1309T>C		intron_variant		1	NM_001134831.2	ENSP00000265602	P2
	ENST00000444302.1	n.123+177A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36371 AN: 152164 Hom.: 9922 Cov.: 33

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.0636

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.0826 AC: 68822 AN: 833060 Hom.: 6343 Cov.: 31 AF XY: 0.0816 AC XY: 31379 AN XY: 384694

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.0495

Gnomad4 EAS exome AF: 0.0606

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.0683

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.240 AC: 36473 AN: 152282 Hom.: 9963 Cov.: 33 AF XY: 0.231 AC XY: 17226 AN XY: 74474

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.0636

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0687

Gnomad4 OTH AF: 0.213

Alfa AF: 0.127 Hom.: 1339

Bravo AF: 0.267

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.035
DANN	Benign	0.45

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: rs7756167; hg19: chr6-135623005;