Variant 11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000190.4(HMBS):c.33+131_33+135dup 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 0.031 ( 285 hom., cov: 0)

Exomes 𝑓: 0.021 ( 1092 hom. )

Consequence

HMBS
NM_000190.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.497

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0309 (2059/66714) while in subpopulation NFE AF= 0.0397 (1435/36188). AF 95% confidence interval is 0.0379. There are 285 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 285 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMBS	NM_000190.4 linkuse as main transcript	c.33+131_33+135dup		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.33+131_33+135dup		intron_variant			NM_000190.4	ENSP00000498786	P3	P08397-1

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

2059

AN:

66678

Hom.:

285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.0217

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.0292

Gnomad SAS

AF:

0.00534

Gnomad FIN

AF:

0.00357

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0235

GnomAD4 exome

AF:

0.0213

AC:

15561

AN:

729152

Hom.:

1092

Cov.:

AF XY:

0.0212

AC XY:

7635

AN XY:

360628

show subpopulations

Gnomad4 AFR exome

AF:

0.00670

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.0427

Gnomad4 SAS exome

AF:

0.0257

Gnomad4 FIN exome

AF:

0.0259

Gnomad4 NFE exome

AF:

0.0213

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0309

AC:

2059

AN:

66714

Hom.:

285

Cov.:

AF XY:

0.0278

AC XY:

821

AN XY:

29494

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.0292

Gnomad4 SAS

AF:

0.00536

Gnomad4 FIN

AF:

0.00357

Gnomad4 NFE

AF:

0.0397

Gnomad4 OTH

AF:

0.0233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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