6-135496997-C-T

Position:

• chr6-135496997-C-T

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.-140+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,264 control chromosomes in the GnomAD database, including 55,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.84 (55907 hom., cov: 32)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.927

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 6-135496997-C-T is Benign according to our data. Variant chr6-135496997-C-T is described in ClinVar as [Benign]. Clinvar id is 1267699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.-140+191G>A		intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.-140+191G>A		intron_variant		1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128554 AN: 152146 Hom.: 55895 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.845 AC: 128613 AN: 152264 Hom.: 55907 Cov.: 32 AF XY: 0.850 AC XY: 63308 AN XY: 74452

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.956

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.852

Alfa AF: 0.853 Hom.: 8081

Bravo AF: 0.829

Asia WGS AF: 0.903 AC: 3137 AN: 3472

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

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.7
DANN	Benign	0.90

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: rs6928455; hg19: chr6-135818135;