Variant rs1784304 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_000190.4(HMBS):c.613-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,609,796 control chromosomes in the GnomAD database, including 57,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5233 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52375 hom. )

Consequence

HMBS
NM_000190.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.00

Variant links:

Genes affected

HMBS (HGNC:4982): (hydroxymethylbilane synthase) This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

HMBS 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=-0.77).

BP6

Variant 11-119092106-C-A is Benign according to our data. Variant chr11-119092106-C-A is described in ClinVar as [Benign]. Clinvar id is 255486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119092106-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMBS	NM_000190.4 linkuse as main transcript	c.613-19C>A		intron_variant		ENST00000652429.1	NP_000181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMBS	ENST00000652429.1 linkuse as main transcript	c.613-19C>A		intron_variant			NM_000190.4	ENSP00000498786	P3	P08397-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38667

AN:

152008

Hom.:

5220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.301

AC:

75561

AN:

251102

Hom.:

12385

AF XY:

0.298

AC XY:

40436

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.281

GnomAD4 exome

AF:

0.260

AC:

379514

AN:

1457670

Hom.:

52375

Cov.:

AF XY:

0.263

AC XY:

190491

AN XY:

725336

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.396

Gnomad4 ASJ exome

AF:

0.314

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.241

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.254

AC:

38711

AN:

152126

Hom.:

5233

Cov.:

AF XY:

0.263

AC XY:

19566

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.479

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.244

Hom.:

6445

Bravo

AF:

0.252

Asia WGS

AF:

0.389

AC:

1355

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Acute intermittent porphyria

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.6

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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