Variant 9-113389247-G-A 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 ENST00000409155.8(ALAD):c.802-141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,405,648 control chromosomes in the GnomAD database, including 15,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1732 hom., cov: 32)

Exomes 𝑓: 0.14 ( 13360 hom. )

Consequence

ALAD
ENST00000409155.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00600

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=-0.87).

BP6

Variant 9-113389247-G-A is Benign according to our data. Variant chr9-113389247-G-A is described in ClinVar as [Benign]. Clinvar id is 1267385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 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.802-141C>T		intron_variant		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.802-141C>T		intron_variant		1	NM_000031.6	ENSP00000386284	P1	P13716-1
ALAD	ENST00000482847.5 linkuse as main transcript	n.1075-141C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21438

AN:

152044

Hom.:

1733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.138

AC:

173262

AN:

1253486

Hom.:

13360

AF XY:

0.142

AC XY:

88527

AN XY:

623392

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.204

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.141

AC:

21439

AN:

152162

Hom.:

1732

Cov.:

AF XY:

0.143

AC XY:

10665

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.134

Hom.:

1982

Bravo

AF:

0.144

Asia WGS

AF:

0.233

AC:

809

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
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

-0.87

CADD

Benign

0.86

DANN

Benign

0.72

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