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

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:

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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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.-406T>C		upstream_gene_variant		ENST00000265602.11	NP_001128303.1	Q8N157-1Q8NER0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11 link	c.-406T>C		upstream_gene_variant		1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

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

Gnomad4 AFR exome

AF:

0.00926

AC:

AN:

432

Gnomad4 AMR exome

AF:

0.0168

AC:

AN:

1012

Gnomad4 ASJ exome

AF:

0.0255

AC:

AN:

1492

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

298

Gnomad4 SAS exome

AF:

0.00764

AC:

156

AN:

20432

Gnomad4 FIN exome

AF:

0.0480

AC:

205

AN:

4268

Gnomad4 NFE exome

AF:

0.0482

AC:

1585

AN:

32878

Gnomad4 Remaining exome

AF:

0.0397

AC:

AN:

2370

Heterozygous variant carriers

169

254

338

423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.00965

AC:

0.00965288

AN:

0.00965288

Gnomad4 AMR

AF:

0.0280

AC:

0.0279812

AN:

0.0279812

Gnomad4 ASJ

AF:

0.0280

AC:

0.02797

AN:

0.02797

Gnomad4 EAS

AF:

0.000194

AC:

0.000193798

AN:

0.000193798

Gnomad4 SAS

AF:

0.00891

AC:

0.00890638

AN:

0.00890638

Gnomad4 FIN

AF:

0.0535

AC:

0.0534603

AN:

0.0534603

Gnomad4 NFE

AF:

0.0523

AC:

0.0522608

AN:

0.0522608

Gnomad4 OTH

AF:

0.0288

AC:

0.028828

AN:

0.028828

Heterozygous variant carriers

259

519

778

1038

1297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 12, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.58

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over