Variant rs818707 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000031.6(ALAD):c.*613G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 161,384 control chromosomes in the GnomAD database, including 906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 852 hom., cov: 32)

Exomes 𝑓: 0.098 ( 54 hom. )

Consequence

ALAD
NM_000031.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

ALAD (HGNC:395): (aminolevulinate dehydratase) The ALAD enzyme is composed of 8 identical subunits and catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is essential for enzymatic activity. ALAD enzymatic activity is inhibited by lead and a defect in the ALAD structural gene can cause increased sensitivity to lead poisoning and acute hepatic porphyria. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ALAD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 9-113387687-C-T is Benign according to our data. Variant chr9-113387687-C-T is described in ClinVar as [Benign]. Clinvar id is 364631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALAD	NM_000031.6 linkuse as main transcript	c.*613G>A		3_prime_UTR_variant	12/12	ENST00000409155.8	NP_000022.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALAD	ENST00000409155.8 linkuse as main transcript	c.*613G>A		3_prime_UTR_variant	12/12	1	NM_000031.6	ENSP00000386284	P1	P13716-1
ALAD	ENST00000482847.5 linkuse as main transcript	n.1879G>A		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14191

AN:

152054

Hom.:

852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.0889

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.0577

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.0979

AC:

902

AN:

9210

Hom.:

Cov.:

AF XY:

0.103

AC XY:

483

AN XY:

4706

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.0717

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.0388

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.0703

Gnomad4 NFE exome

AF:

0.0996

Gnomad4 OTH exome

AF:

0.0897

GnomAD4 genome

AF:

0.0932

AC:

14186

AN:

152174

Hom.:

852

Cov.:

AF XY:

0.0930

AC XY:

6919

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.0888

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.0578

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.121

Hom.:

720

Bravo

AF:

0.0894

Asia WGS

AF:

0.110

AC:

381

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Porphobilinogen synthase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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