rs6912933

Variant names:

• chr6-135306396-G-A
• rs6912933
• NM_001134831.2:c.3427-5838C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-135306396-G-A
• chr6-135306396-G-C
• chr6-135306396-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134831.2(AHI1):​c.3427-5838C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,876 control chromosomes in the GnomAD database, including 17,533 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 0.46 (17533 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Joubert syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ENSG00000234084 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3427-5838C>T		intron_variant	Intron 26 of 28	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3427-5838C>T		intron_variant	Intron 26 of 28	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69714 AN: 151758 Hom.: 17533 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.459 AC: 69724 AN: 151876 Hom.: 17533 Cov.: 31 AF XY: 0.466 AC XY: 34571 AN XY: 74214

African (AFR) AF: 0.231 AC: 9551 AN: 41402

American (AMR) AF: 0.549 AC: 8379 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2024 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2905 AN: 5156

South Asian (SAS) AF: 0.491 AC: 2359 AN: 4804

European-Finnish (FIN) AF: 0.598 AC: 6307 AN: 10546

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36399 AN: 67920

Other (OTH) AF: 0.479 AC: 1013 AN: 2116

Alfa AF: 0.489 Hom.: 5432

Bravo AF: 0.446

Asia WGS AF: 0.503 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6912933; hg19: chr6-135627534;