Variant chr3-52202746-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000688.6(ALAS1):c.427+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,610,236 control chromosomes in the GnomAD database, including 209,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16741 hom., cov: 32)

Exomes 𝑓: 0.51 ( 192975 hom. )

Consequence

ALAS1
NM_000688.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.158

Variant links:

Genes affected

ALAS1 (HGNC:396): (5'-aminolevulinate synthase 1) This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

ALAS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALAS1	NM_000688.6 linkuse as main transcript	c.427+12G>A		intron_variant		ENST00000484952.6	NP_000679.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ALAS1	ENST00000484952.6 linkuse as main transcript	c.427+12G>A	intron_variant	1	NM_000688.6	ENSP00000418779	P1	P13196-1
ALAS1	ENST00000310271.6 linkuse as main transcript	c.427+12G>A	intron_variant	1		ENSP00000309259	P1	P13196-1
ALAS1	ENST00000469224.5 linkuse as main transcript	c.427+12G>A	intron_variant	1		ENSP00000417719	P1	P13196-1
ALAS1	ENST00000394965.6 linkuse as main transcript	c.427+12G>A	intron_variant	2		ENSP00000378416	P1	P13196-1

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69514

AN:

151950

Hom.:

16731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.483

GnomAD3 exomes

AF:

0.486

AC:

118736

AN:

244540

Hom.:

29497

AF XY:

0.484

AC XY:

64110

AN XY:

132454

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.543

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.497

Gnomad NFE exome

AF:

0.536

Gnomad OTH exome

AF:

0.507

GnomAD4 exome

AF:

0.512

AC:

745918

AN:

1458168

Hom.:

192975

Cov.:

AF XY:

0.508

AC XY:

368459

AN XY:

724802

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.521

Gnomad4 ASJ exome

AF:

0.546

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.531

Gnomad4 OTH exome

AF:

0.486

GnomAD4 genome

AF:

0.457

AC:

69559

AN:

152068

Hom.:

16741

Cov.:

AF XY:

0.454

AC XY:

33706

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.534

Gnomad4 OTH

AF:

0.484

Alfa

AF:

0.521

Hom.:

44453

Bravo

AF:

0.455

Asia WGS

AF:

0.403

AC:

1401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.7

DANN

Benign

0.66

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over