rs2757643

Variant names:

• chr6-135440095-A-C
• rs2757643
• NM_001134831.2:c.1913-1597T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-135440095-A-C
• chr6-135440095-A-G
• chr6-135440095-A-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.1913-1597T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,014 control chromosomes in the GnomAD database, including 17,735 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 0.44 (17735 hom., cov: 31)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2	c.1913-1597T>G		intron_variant	Intron 14 of 28	ENST00000265602.11	NP_001128303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11	c.1913-1597T>G		intron_variant	Intron 14 of 28	1	NM_001134831.2	ENSP00000265602.6

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66755 AN: 151896 Hom.: 17738 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.439 AC: 66753 AN: 152014 Hom.: 17735 Cov.: 31 AF XY: 0.449 AC XY: 33346 AN XY: 74322

African (AFR) AF: 0.117 AC: 4859 AN: 41470

American (AMR) AF: 0.538 AC: 8219 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1997 AN: 3466

East Asian (EAS) AF: 0.579 AC: 2994 AN: 5168

South Asian (SAS) AF: 0.493 AC: 2370 AN: 4810

European-Finnish (FIN) AF: 0.661 AC: 6986 AN: 10568

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37602 AN: 67942

Other (OTH) AF: 0.446 AC: 942 AN: 2114

Alfa AF: 0.471 Hom.: 6004

Bravo AF: 0.418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.69
PhyloP100		0.28
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: rs2757643; hg19: chr6-135761233; COSMIC: COSV55625306;