Variant rs1805316 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.262-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,612,644 control chromosomes in the GnomAD database, including 5,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.082 ( 550 hom., cov: 33)

Exomes 𝑓: 0.081 ( 5320 hom. )

Consequence

ALAD
NM_000031.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.83

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

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 9-113390970-A-G is Benign according to our data. Variant chr9-113390970-A-G is described in ClinVar as [Benign]. Clinvar id is 1227501.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 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.262-37T>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.262-37T>C		intron_variant		1	NM_000031.6	P1	P13716-1

Frequencies

GnomAD3 genomes

AF:

0.0818

AC:

12450

AN:

152144

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0950

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0400

Gnomad ASJ

AF:

0.0689

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0873

Gnomad OTH

AF:

0.0587

GnomAD3 exomes

AF:

0.0700

AC:

17481

AN:

249572

Hom.:

743

AF XY:

0.0703

AC XY:

9496

AN XY:

135068

show subpopulations

Gnomad AFR exome

AF:

0.0971

Gnomad AMR exome

AF:

0.0310

Gnomad ASJ exome

AF:

0.0673

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0344

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.0880

Gnomad OTH exome

AF:

0.0642

GnomAD4 exome

AF:

0.0815

AC:

118999

AN:

1460382

Hom.:

5320

Cov.:

AF XY:

0.0801

AC XY:

58155

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.0939

Gnomad4 AMR exome

AF:

0.0325

Gnomad4 ASJ exome

AF:

0.0646

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0342

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.0881

Gnomad4 OTH exome

AF:

0.0748

GnomAD4 genome

AF:

0.0818

AC:

12457

AN:

152262

Hom.:

550

Cov.:

AF XY:

0.0818

AC XY:

6092

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0949

Gnomad4 AMR

AF:

0.0399

Gnomad4 ASJ

AF:

0.0689

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0311

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.0873

Gnomad4 OTH

AF:

0.0581

Alfa

AF:

0.0848

Hom.:

184

Bravo

AF:

0.0749

Asia WGS

AF:

0.0180

AC:

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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.6

DANN

Benign

0.79

BranchPoint Hunter

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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