rs9402709

Variant names:

• chr6-135492113-G-T
• rs9402709
• NM_001134831.2:c.10+115C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-135492113-G-T
• chr6-135492113-G-A
• chr6-135492113-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001134831.2(AHI1):​c.10+115C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 664,456 control chromosomes in the GnomAD database, including 257,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (47816 hom., cov: 32)
  • Exomes 𝑓: 0.90 (209379 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.662
• Publications: 1 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, Laboratory for Molecular Medicine, ClinGen, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-135492113-G-T is Benign according to our data. Variant chr6-135492113-G-T is described in ClinVar as Benign. ClinVar VariationId is 673960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134831.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	NM_001134831.2	MANE Select	c.10+115C>A		intron	N/A	NP_001128303.1	Q8N157-1
	AHI1	NM_001134830.2		c.10+115C>A		intron	N/A	NP_001128302.1	Q8N157-1
	AHI1	NM_001350503.2		c.10+115C>A		intron	N/A	NP_001337432.1	Q8N157-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	ENST00000265602.11	TSL:1 MANE Select	c.10+115C>A		intron	N/A	ENSP00000265602.6	Q8N157-1
	AHI1	ENST00000367800.8	TSL:1	c.10+115C>A		intron	N/A	ENSP00000356774.4	Q8N157-1
	AHI1	ENST00000457866.6	TSL:1	c.10+115C>A		intron	N/A	ENSP00000388650.2	Q8N157-1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113609 AN: 151990 Hom.: 47815 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.772

GnomAD4 exome AF: 0.899 AC: 460469 AN: 512350 Hom.: 209379 AF XY: 0.901 AC XY: 235491 AN XY: 261318

African (AFR) AF: 0.314 AC: 3921 AN: 12506

American (AMR) AF: 0.870 AC: 11948 AN: 13726

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 12351 AN: 13202

East Asian (EAS) AF: 0.922 AC: 25299 AN: 27434

South Asian (SAS) AF: 0.908 AC: 20643 AN: 22744

European-Finnish (FIN) AF: 0.951 AC: 36736 AN: 38612

Middle Eastern (MID) AF: 0.908 AC: 1772 AN: 1952

European-Non Finnish (NFE) AF: 0.914 AC: 325832 AN: 356672

Other (OTH) AF: 0.861 AC: 21967 AN: 25502

GnomAD4 genome AF: 0.747 AC: 113639 AN: 152106 Hom.: 47816 Cov.: 32 AF XY: 0.756 AC XY: 56204 AN XY: 74358

African (AFR) AF: 0.320 AC: 13223 AN: 41386

American (AMR) AF: 0.850 AC: 13006 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3264 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4691 AN: 5186

South Asian (SAS) AF: 0.914 AC: 4410 AN: 4824

European-Finnish (FIN) AF: 0.956 AC: 10138 AN: 10606

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62152 AN: 68020

Other (OTH) AF: 0.769 AC: 1622 AN: 2110

Alfa AF: 0.820 Hom.: 6804

Bravo AF: 0.719

Asia WGS AF: 0.827 AC: 2868 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Joubert syndrome 3 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.51
PhyloP100		0.66
PromoterAI		-0.012	Neutral
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: rs9402709; hg19: chr6-135813251; COSMIC: COSV99663880; COSMIC: COSV99663880;