rs780835322

chr6-135411341-A-AGTCchr6-135411341-A-ATTTAAAACTTTAAAAAAGTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001134831.2(AHI1):c.2961+6_2961+7insGAC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.012 in 1,611,070 control chromosomes in the GnomAD database, including 139 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (9 hom., cov: 32)
  • Exomes 𝑓: 0.012 (130 hom.)
• Consequence: AHI1 NM_001134831.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.79

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 -10 ACMG points.

• BP6: Variant 6-135411341-A-AGTC is Benign according to our data. Variant chr6-135411341-A-AGTC is described in ClinVar as [Benign]. Clinvar id is 220132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0123 (17879/1458706) while in subpopulation MID AF= 0.0222 (128/5764). AF 95% confidence interval is 0.0191. There are 130 homozygotes in gnomad4_exome. There are 8914 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHI1	NM_001134831.2	c.2961+6_2961+7insGAC		splice_region_variant, intron_variant		ENST00000265602.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHI1	ENST00000265602.11	c.2961+6_2961+7insGAC		splice_region_variant, intron_variant		1	NM_001134831.2	P2

Frequencies

GnomAD3 genomes AF: 0.00978 AC: 1489 AN: 152246 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00241

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.00791

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.0110 AC: 2725 AN: 248044 Hom.: 16 AF XY: 0.0110 AC XY: 1483 AN XY: 134544

Gnomad AFR exome AF: 0.00194

Gnomad AMR exome AF: 0.00815

Gnomad ASJ exome AF: 0.00979

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0109

Gnomad FIN exome AF: 0.0145

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0152

GnomAD4 exome AF: 0.0123 AC: 17879 AN: 1458706 Hom.: 130 Cov.: 30 AF XY: 0.0123 AC XY: 8914 AN XY: 725680

Gnomad4 AFR exome AF: 0.00189

Gnomad4 AMR exome AF: 0.00863

Gnomad4 ASJ exome AF: 0.00947

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.0139

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.00986

GnomAD4 genome AF: 0.00976 AC: 1487 AN: 152364 Hom.: 9 Cov.: 32 AF XY: 0.00992 AC XY: 739 AN XY: 74510

Gnomad4 AFR AF: 0.00240

Gnomad4 AMR AF: 0.00790

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.0141

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0140 Hom.: 2

Asia WGS AF: 0.00346 AC: 12 AN: 3478

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

Nov 26, 2019

This variant is associated with the following publications: (PMID: 31054281) -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs780835322; hg19: chr6-135732479;