dbSNP rs13197301: AHI1:c.-2303T>C (chr6-135497787-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.865

Publications

1 publications found

Variant links:

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 links:

AHI1-DT (HGNC:32526): (AHI1 divergent transcript)

AHI1-DT links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000681022.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AHI1	NM_001134831.2	MANE Select	c.-406T>C	upstream_gene	N/A	NP_001128303.1	Q8N157-1
AHI1	NM_001134830.2		c.-259T>C	upstream_gene	N/A	NP_001128302.1	Q8N157-1
AHI1	NM_001350503.2		c.-515T>C	upstream_gene	N/A	NP_001337432.1	Q8N157-1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
AHI1	ENST00000681022.1	c.-2303T>C	5_prime_UTR	Exon 1 of 27	ENSP00000505121.1	Q8N157-1
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	E9PI51

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5225

AN:

152088

Hom.:

113

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0287

AC XY:

1132

AN XY:

39498

show subpopulations

African (AFR)

AF:

0.00926

AC:

AN:

432

American (AMR)

AF:

0.0168

AC:

AN:

1012

Ashkenazi Jewish (ASJ)

AF:

0.0255

AC:

AN:

1492

East Asian (EAS)

AF:

0.00

AC:

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:

AN:

184

European-Non Finnish (NFE)

AF:

0.0482

AC:

1585

AN:

32878

Other (OTH)

AF:

0.0397

AC:

AN:

2370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

169

254

338

423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0343

AC:

5222

AN:

152206

Hom.:

114

Cov.:

AF XY:

0.0339

AC XY:

2525

AN XY:

74432

show subpopulations

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:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5160

South Asian (SAS)

AF:

0.00891

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0535

AC:

567

AN:

10606

Middle Eastern (MID)

AF:

0.0445

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0523

AC:

3553

AN:

67986

Other (OTH)

AF:

0.0288

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

259

519

778

1038

1297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0312

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.00434

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

0.86

PromoterAI

-0.099

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over