Variant 3-52204661-C-T 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.578-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,577,098 control chromosomes in the GnomAD database, including 210,280 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.46 ( 17131 hom., cov: 33)

Exomes 𝑓: 0.52 ( 193149 hom. )

Consequence

ALAS1
NM_000688.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.793

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 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.578-32C>T		intron_variant		ENST00000484952.6	NP_000679.1	P13196-1Q5JAM2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ALAS1	ENST00000484952.6 linkuse as main transcript	c.578-32C>T	intron_variant	1	NM_000688.6	ENSP00000418779.1	P13196-1
ALAS1	ENST00000310271.6 linkuse as main transcript	c.578-32C>T	intron_variant	1		ENSP00000309259.2	P13196-1
ALAS1	ENST00000469224.5 linkuse as main transcript	c.578-32C>T	intron_variant	1		ENSP00000417719.1	P13196-1
ALAS1	ENST00000394965.6 linkuse as main transcript	c.578-32C>T	intron_variant	2		ENSP00000378416.2	P13196-1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70398

AN:

152060

Hom.:

17120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.483

GnomAD3 exomes

AF:

0.491

AC:

117292

AN:

238826

Hom.:

29396

AF XY:

0.491

AC XY:

63654

AN XY:

129720

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.545

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.409

Gnomad FIN exome

AF:

0.497

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.518

AC:

737924

AN:

1424920

Hom.:

193149

Cov.:

AF XY:

0.515

AC XY:

365408

AN XY:

709256

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.548

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.537

Gnomad4 OTH exome

AF:

0.492

GnomAD4 genome

AF:

0.463

AC:

70437

AN:

152178

Hom.:

17131

Cov.:

AF XY:

0.459

AC XY:

34156

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.486

Gnomad4 NFE

AF:

0.539

Gnomad4 OTH

AF:

0.485

Alfa

AF:

0.505

Hom.:

4711

Bravo

AF:

0.459

Asia WGS

AF:

0.413

AC:

1436

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

0.39

DANN

Benign

0.36

BranchPoint Hunter

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over