Variant X-55009124-T-G 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 NM_000032.5(ALAS2):c.*56A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,172,771 control chromosomes in the GnomAD database, including 898 homozygotes. There are 3,456 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 457 hom., 1739 hem., cov: 22)

Exomes 𝑓: 0.0062 ( 441 hom. 1717 hem. )

Consequence

ALAS2
NM_000032.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.247

Variant links:

Genes affected

ALAS2 (HGNC:397): (5'-aminolevulinate synthase 2) The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ALAS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-55009124-T-G is Benign according to our data. Variant chrX-55009124-T-G is described in ClinVar as [Benign]. Clinvar id is 368590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ALAS2	NM_000032.5 linkuse as main transcript	c.*56A>C	3_prime_UTR_variant	11/11	ENST00000650242.1	NP_000023.2
ALAS2	NM_001037967.4 linkuse as main transcript	c.*56A>C	3_prime_UTR_variant	10/10		NP_001033056.1
ALAS2	NM_001037968.4 linkuse as main transcript	c.*56A>C	3_prime_UTR_variant	11/11		NP_001033057.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALAS2	ENST00000650242.1 linkuse as main transcript	c.*56A>C	3_prime_UTR_variant	11/11		NM_000032.5	ENSP00000497236	P1	P22557-1
ALAS2	ENST00000335854.8 linkuse as main transcript	c.*56A>C	3_prime_UTR_variant	10/10	2		ENSP00000337131		P22557-2
ALAS2	ENST00000396198.7 linkuse as main transcript	c.*56A>C	3_prime_UTR_variant	11/11	5		ENSP00000379501		P22557-4
ALAS2	ENST00000498636.1 linkuse as main transcript	c.*118A>C	3_prime_UTR_variant	5/5	3		ENSP00000495662

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

6313

AN:

111429

Hom.:

456

Cov.:

AF XY:

0.0514

AC XY:

1730

AN XY:

33683

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.000753

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000378

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000678

Gnomad OTH

AF:

0.0479

GnomAD4 exome

AF:

0.00620

AC:

6582

AN:

1061287

Hom.:

441

Cov.:

AF XY:

0.00509

AC XY:

1717

AN XY:

337303

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.00958

Gnomad4 ASJ exome

AF:

0.000694

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000668

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000241

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0568

AC:

6329

AN:

111484

Hom.:

457

Cov.:

AF XY:

0.0515

AC XY:

1739

AN XY:

33748

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.000753

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000379

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000678

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0150

Hom.:

375

Bravo

AF:

0.0650

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

X-linked sideroblastic anemia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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