6-135442447-T-C

Position:

• chr6-135442447-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001134831.2(AHI1):​c.1912+135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 960,342 control chromosomes in the GnomAD database, including 465,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (74315 hom., cov: 33)
  • Exomes 𝑓: 0.98 (391035 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.706

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]

AHI1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-135442447-T-C is Benign according to our data. Variant chr6-135442447-T-C is described in ClinVar as [Benign]. Clinvar id is 1246420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.1912+135A>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.1912+135A>G		intron_variant		1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150336 AN: 152208 Hom.: 74257 Cov.: 33

Gnomad AFR AF: 0.995

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.989

GnomAD4 exome AF: 0.984 AC: 794909 AN: 808016 Hom.: 391035 AF XY: 0.984 AC XY: 387075 AN XY: 393452

Gnomad4 AFR exome AF: 0.997

Gnomad4 AMR exome AF: 0.993

Gnomad4 ASJ exome AF: 0.990

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.982

Gnomad4 OTH exome AF: 0.987

GnomAD4 genome AF: 0.988 AC: 150453 AN: 152326 Hom.: 74315 Cov.: 33 AF XY: 0.988 AC XY: 73596 AN XY: 74484

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.980

Gnomad4 OTH AF: 0.989

Alfa AF: 0.974 Hom.: 3894

Bravo AF: 0.989

Asia WGS AF: 0.997 AC: 3466 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.60

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: rs2614274; hg19: chr6-135763585;