rs7741046

Variant names:

• chr6-135293564-C-G
• rs7741046
• NM_001134831.2:c.3486-3039G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-135293564-C-G
• chr6-135293564-C-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.3486-3039G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,878 control chromosomes in the GnomAD database, including 10,349 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 0.24 (10349 hom., cov: 32)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.3486-3039G>C		intron_variant	Intron 27 of 28	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.3486-3039G>C		intron_variant	Intron 27 of 28	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36922 AN: 151762 Hom.: 10309 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.244 AC: 37022 AN: 151878 Hom.: 10349 Cov.: 32 AF XY: 0.236 AC XY: 17487 AN XY: 74232

African (AFR) AF: 0.688 AC: 28479 AN: 41364

American (AMR) AF: 0.136 AC: 2069 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3468

East Asian (EAS) AF: 0.0672 AC: 348 AN: 5180

South Asian (SAS) AF: 0.109 AC: 524 AN: 4816

European-Finnish (FIN) AF: 0.0242 AC: 255 AN: 10522

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.0686 AC: 4664 AN: 67958

Other (OTH) AF: 0.220 AC: 462 AN: 2102

Alfa AF: 0.0377 Hom.: 65

Bravo AF: 0.271

Asia WGS AF: 0.172 AC: 597 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.35
PhyloP100		-0.91
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: rs7741046; hg19: chr6-135614702; COSMIC: COSV55634887;