NM_000190.4:c.606G>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000190.4(HMBS):c.606G>T(p.Val202Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,546,376 control chromosomes in the GnomAD database, including 56,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4502 hom., cov: 32)

Exomes 𝑓: 0.27 ( 52065 hom. )

Consequence

HMBS
NM_000190.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.11

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 11-119091520-G-T is Benign according to our data. Variant chr11-119091520-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 255485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119091520-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMBS	NM_000190.4 link	c.606G>T	p.Val202Val	synonymous_variant	Exon 9 of 14	ENST00000652429.1	NP_000181.2	P08397-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMBS	ENST00000652429.1 link	c.606G>T	p.Val202Val	synonymous_variant	Exon 9 of 14		NM_000190.4	ENSP00000498786.1		P08397-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35815

AN:

152088

Hom.:

4499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.235

AC:

36676

AN:

155800

Hom.:

4642

AF XY:

0.238

AC XY:

19580

AN XY:

82124

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.269

AC:

375557

AN:

1394170

Hom.:

52065

Cov.:

AF XY:

0.268

AC XY:

184678

AN XY:

688072

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.159

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.251

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.235

AC:

35821

AN:

152206

Hom.:

4502

Cov.:

AF XY:

0.234

AC XY:

17419

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.342

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.250

Hom.:

3499

Bravo

AF:

0.228

Asia WGS

AF:

0.187

AC:

654

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Acute intermittent porphyria

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital disorder of glycosylation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.1

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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