rs4896142

Positions:

• chr6-135301681-T-G

Variant summary

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

The NM_001134831.2(AHI1):​c.3427-1123A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 985,174 control chromosomes in the GnomAD database, including 108,675 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 0.55 (26493 hom., cov: 33)
  • Exomes 𝑓: 0.44 (82182 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.3427-1123A>C		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.3427-1123A>C		intron_variant		1	NM_001134831.2	P2
	ENST00000444302.1	n.114T>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83411 AN: 152042 Hom.: 26430 Cov.: 33

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.438 AC: 365077 AN: 833016 Hom.: 82182 Cov.: 33 AF XY: 0.437 AC XY: 167952 AN XY: 384674

Gnomad4 AFR exome AF: 0.917

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.456

GnomAD4 genome AF: 0.549 AC: 83531 AN: 152158 Hom.: 26493 Cov.: 33 AF XY: 0.542 AC XY: 40338 AN XY: 74414

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.533

Alfa AF: 0.445 Hom.: 15438

Bravo AF: 0.572

Asia WGS AF: 0.490 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.70

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: rs4896142; hg19: chr6-135622819;