rs11964449

Variant names:

• chr6-135448551-A-G
• rs11964449
• NM_001134831.2:c.1441-76T>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.1441-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,167,010 control chromosomes in the GnomAD database, including 2,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (1096 hom., cov: 32)
  • Exomes 𝑓: 0.026 (926 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

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=-0.81).
• BP6: Variant 6-135448551-A-G is Benign according to our data. Variant chr6-135448551-A-G is described in ClinVar as [Benign]. Clinvar id is 1258760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.1441-76T>C		intron_variant	Intron 11 of 28	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.1441-76T>C		intron_variant	Intron 11 of 28	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11775 AN: 152188 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0258 AC: 26169 AN: 1014704 Hom.: 926 AF XY: 0.0253 AC XY: 12543 AN XY: 495164

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.0233

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.0406

Gnomad4 SAS exome AF: 0.0384

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.0186

Gnomad4 OTH exome AF: 0.0393

GnomAD4 genome AF: 0.0774 AC: 11794 AN: 152306 Hom.: 1096 Cov.: 32 AF XY: 0.0749 AC XY: 5579 AN XY: 74472

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.0697 Hom.: 210

Bravo AF: 0.0877

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.82

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: rs11964449; hg19: chr6-135769689;