Variant rs1805313 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000031.6(ALAD):c.931+66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,611,600 control chromosomes in the GnomAD database, including 104,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 13042 hom., cov: 33)

Exomes 𝑓: 0.35 ( 91390 hom. )

Consequence

ALAD
NM_000031.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00400

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-113388911-A-G is Benign according to our data. Variant chr9-113388911-A-G is described in ClinVar as [Benign]. Clinvar id is 1180338.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALAD	NM_000031.6 linkuse as main transcript	c.931+66T>C		intron_variant		ENST00000409155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALAD	ENST00000409155.8 linkuse as main transcript	c.931+66T>C		intron_variant		1	NM_000031.6	P1	P13716-1
ALAD	ENST00000482847.5 linkuse as main transcript	n.1204+66T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61322

AN:

151966

Hom.:

13022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.413

GnomAD4 exome

AF:

0.346

AC:

504797

AN:

1459516

Hom.:

91390

AF XY:

0.347

AC XY:

252044

AN XY:

726100

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.645

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.418

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.404

AC:

61380

AN:

152084

Hom.:

13042

Cov.:

AF XY:

0.405

AC XY:

30102

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.490

Gnomad4 AMR

AF:

0.538

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.419

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.352

Hom.:

22543

Bravo

AF:

0.426

Asia WGS

AF:

0.448

AC:

1554

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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