chr6-135497542-G-A

Position:

• chr6-135497542-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001134831.2(AHI1):​c.-202+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 153,322 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (22 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.244

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-DT (HGNC:32526): (AHI1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-135497542-G-A is Benign according to our data. Variant chr6-135497542-G-A is described in ClinVar as [Benign]. Clinvar id is 1246550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.-202+41C>T		intron_variant		ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.-202+41C>T		intron_variant		1	NM_001134831.2	ENSP00000265602	P2

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 742 AN: 152180 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00195 AC: 2 AN: 1026 Hom.: 0 Cov.: 0 AF XY: 0.00258 AC XY: 2 AN XY: 774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.00139

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00485 AC: 739 AN: 152296 Hom.: 22 Cov.: 33 AF XY: 0.00769 AC XY: 573 AN XY: 74478

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00793

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0584

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00324 Hom.: 0

Bravo AF: 0.000631

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 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.0
DANN	Benign	0.96
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.9

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: rs6570012; hg19: chr6-135818680;