rs9494209

Variant names:

• chr6-135285617-C-G
• rs9494209
• NM_001134831.2:c.*28G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-135285617-C-G
• chr6-135285617-C-T

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.*28G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,602,404 control chromosomes in the GnomAD database, including 6,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1583 hom., cov: 32)
  • Exomes 𝑓: 0.071 (4640 hom.)
• Consequence: AHI1 NM_001134831.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.575
• Publications: 8 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

ENSG00000234084 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-135285617-C-G is Benign according to our data. Variant chr6-135285617-C-G is described in ClinVar as Benign. ClinVar VariationId is 260835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 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.*28G>C		3_prime_UTR	Exon 29 of 29	NP_001128303.1	Q8N157-1
	AHI1	NM_001134830.2		c.*28G>C		3_prime_UTR	Exon 27 of 27	NP_001128302.1	Q8N157-1
	AHI1	NM_001350503.2		c.*28G>C		3_prime_UTR	Exon 29 of 29	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.*28G>C		3_prime_UTR	Exon 29 of 29	ENSP00000265602.6	Q8N157-1
	AHI1	ENST00000367800.8	TSL:1	c.*28G>C		3_prime_UTR	Exon 27 of 27	ENSP00000356774.4	Q8N157-1
	AHI1	ENST00000457866.6	TSL:1	c.*28G>C		3_prime_UTR	Exon 28 of 28	ENSP00000388650.2	Q8N157-1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17652 AN: 152076 Hom.: 1572 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0730 AC: 17639 AN: 241654 AF XY: 0.0711

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.0688

Gnomad ASJ exome AF: 0.0268

Gnomad EAS exome AF: 0.0610

Gnomad FIN exome AF: 0.0250

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0622

GnomAD4 exome AF: 0.0708 AC: 102717 AN: 1450210 Hom.: 4640 Cov.: 29 AF XY: 0.0707 AC XY: 51028 AN XY: 721362

African (AFR) AF: 0.257 AC: 8475 AN: 32982

American (AMR) AF: 0.0715 AC: 3154 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 744 AN: 26034

East Asian (EAS) AF: 0.0807 AC: 3187 AN: 39508

South Asian (SAS) AF: 0.0986 AC: 8397 AN: 85164

European-Finnish (FIN) AF: 0.0281 AC: 1478 AN: 52542

Middle Eastern (MID) AF: 0.0659 AC: 378 AN: 5736

European-Non Finnish (NFE) AF: 0.0654 AC: 72261 AN: 1104202

Other (OTH) AF: 0.0775 AC: 4643 AN: 59930

GnomAD4 genome AF: 0.116 AC: 17703 AN: 152194 Hom.: 1583 Cov.: 32 AF XY: 0.112 AC XY: 8331 AN XY: 74422

African (AFR) AF: 0.250 AC: 10375 AN: 41496

American (AMR) AF: 0.0841 AC: 1286 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.0673 AC: 349 AN: 5186

South Asian (SAS) AF: 0.108 AC: 519 AN: 4826

European-Finnish (FIN) AF: 0.0243 AC: 258 AN: 10610

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0666 AC: 4532 AN: 68006

Other (OTH) AF: 0.110 AC: 233 AN: 2110

Alfa AF: 0.0385 Hom.: 43

Bravo AF: 0.125

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.59
PhyloP100		0.57
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: rs9494209; hg19: chr6-135606755; COSMIC: COSV55624645;