Genetic Variant NM_000190.4:c.33+130_33+135dupTTTTTT (chr11-119085172-C-CTTTTTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000190.4(HMBS):c.33+130_33+135dupTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.052 ( 560 hom., cov: 0)

Exomes 𝑓: 0.023 ( 1382 hom. )

Consequence

HMBS
NM_000190.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.497

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

acute intermittent porphyria
Inheritance: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

HMBS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMBS	NM_000190.4 link	c.33+130_33+135dupTTTTTT		intron_variant	Intron 1 of 13	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.33+106_33+107insTTTTTT		intron_variant	Intron 1 of 13		NM_000190.4	ENSP00000498786.1		P08397-1

Frequencies

GnomAD3 genomes

AF:

0.0517

AC:

3443

AN:

66638

Hom.:

560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.0739

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0489

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0256

Gnomad NFE

AF:

0.0643

Gnomad OTH

AF:

0.0657

GnomAD4 exome

AF:

0.0231

AC:

16867

AN:

729510

Hom.:

1382

Cov.:

AF XY:

0.0231

AC XY:

8348

AN XY:

360790

show subpopulations

African (AFR)

AF:

0.00654

AC:

120

AN:

18358

American (AMR)

AF:

0.0158

AC:

186

AN:

11794

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

169

AN:

10344

East Asian (EAS)

AF:

0.0521

AC:

405

AN:

7776

South Asian (SAS)

AF:

0.0295

AC:

1472

AN:

49926

European-Finnish (FIN)

AF:

0.0273

AC:

309

AN:

11312

Middle Eastern (MID)

AF:

0.00940

AC:

AN:

1914

European-Non Finnish (NFE)

AF:

0.0229

AC:

13527

AN:

590600

Other (OTH)

AF:

0.0240

AC:

661

AN:

27486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

405

811

1216

1622

2027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0516

AC:

3443

AN:

66676

Hom.:

560

Cov.:

AF XY:

0.0483

AC XY:

1425

AN XY:

29478

show subpopulations

African (AFR)

AF:

0.0172

AC:

316

AN:

18382

American (AMR)

AF:

0.0406

AC:

194

AN:

4784

Ashkenazi Jewish (ASJ)

AF:

0.0683

AC:

146

AN:

2138

East Asian (EAS)

AF:

0.207

AC:

290

AN:

1400

South Asian (SAS)

AF:

0.0491

AC:

AN:

1304

European-Finnish (FIN)

AF:

0.0143

AC:

AN:

1116

Middle Eastern (MID)

AF:

0.0270

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0643

AC:

2325

AN:

36160

Other (OTH)

AF:

0.0653

AC:

AN:

858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.612

Heterozygous variant carriers

135

202

270

337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0165

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over