rs13197301

Variant names:

• chr6-135497787-A-G
• rs13197301
• ENST00000681022.1:c.-2303T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-135497787-A-G
• chr6-135497787-A-T

Variant summary

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

The ENST00000681022.1(AHI1):​c.-2303T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 215,572 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (114 hom., cov: 32)
  • Exomes 𝑓: 0.033 (57 hom.)
• Consequence: AHI1 ENST00000681022.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.865
• 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-DT (HGNC:32526): (AHI1 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-135497787-A-G is Benign according to our data. Variant chr6-135497787-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1186019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681022.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	NM_001134831.2	MANE Select	c.-406T>C		upstream_gene	N/A	NP_001128303.1
	AHI1	NM_001134830.2		c.-259T>C		upstream_gene	N/A	NP_001128302.1
	AHI1	NM_001350503.2		c.-515T>C		upstream_gene	N/A	NP_001337432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	ENST00000681022.1		c.-2303T>C		5_prime_UTR	Exon 1 of 27	ENSP00000505121.1
	AHI1	ENST00000941465.1		c.-344T>C		5_prime_UTR	Exon 1 of 28	ENSP00000611524.1
	AHI1	ENST00000680033.1		c.-2303T>C		5_prime_UTR	Exon 1 of 3	ENSP00000506426.1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5225 AN: 152088 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.00968

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0523

Gnomad OTH AF: 0.0291

GnomAD2 exomes AF: 0.0300 AC: 131 AN: 4366 AF XY: 0.0289

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0174

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0549

Gnomad NFE exome AF: 0.0490

Gnomad OTH exome AF: 0.0417

GnomAD4 exome AF: 0.0331 AC: 2100 AN: 63366 Hom.: 57 Cov.: 0 AF XY: 0.0287 AC XY: 1132 AN XY: 39498

African (AFR) AF: 0.00926 AC: 4 AN: 432

American (AMR) AF: 0.0168 AC: 17 AN: 1012

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 38 AN: 1492

East Asian (EAS) AF: 0.00 AC: 0 AN: 298

South Asian (SAS) AF: 0.00764 AC: 156 AN: 20432

European-Finnish (FIN) AF: 0.0480 AC: 205 AN: 4268

Middle Eastern (MID) AF: 0.00543 AC: 1 AN: 184

European-Non Finnish (NFE) AF: 0.0482 AC: 1585 AN: 32878

Other (OTH) AF: 0.0397 AC: 94 AN: 2370

GnomAD4 genome AF: 0.0343 AC: 5222 AN: 152206 Hom.: 114 Cov.: 32 AF XY: 0.0339 AC XY: 2525 AN XY: 74432

African (AFR) AF: 0.00965 AC: 401 AN: 41542

American (AMR) AF: 0.0280 AC: 428 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4828

European-Finnish (FIN) AF: 0.0535 AC: 567 AN: 10606

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0523 AC: 3553 AN: 67986

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0312 Hom.: 36

Bravo AF: 0.0319

Asia WGS AF: 0.00434 AC: 15 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		0.86
PromoterAI		-0.099	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13197301; hg19: chr6-135818925;