6-135325554-T-C

Variant names:

• chr6-135325554-T-C
• rs4896144
• NM_001134831.2:c.3166-2230A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134831.2(AHI1):​c.3166-2230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,274 control chromosomes in the GnomAD database, including 67,106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (67106 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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]

ENSG00000287094 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3166-2230A>G		intron_variant	Intron 24 of 28	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3166-2230A>G		intron_variant	Intron 24 of 28	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142759 AN: 152156 Hom.: 67044 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.938 AC: 142880 AN: 152274 Hom.: 67106 Cov.: 31 AF XY: 0.938 AC XY: 69848 AN XY: 74450

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.936

Alfa AF: 0.923 Hom.: 16203

Bravo AF: 0.942

Asia WGS AF: 0.930 AC: 3235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.5
DANN	Benign	0.69

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: rs4896144; hg19: chr6-135646692; COSMIC: COSV55624911; COSMIC: COSV55624911;