11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000190.4(HMBS):c.33+130_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 0.052 (560 hom., cov: 0)
  • Exomes 𝑓: 0.023 (1382 hom.)
• Consequence: HMBS NM_000190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HMBS	NM_000190.4	c.33+130_33+135dup		intron_variant		ENST00000652429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBS	ENST00000652429.1	c.33+130_33+135dup		intron_variant			NM_000190.4	P3

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 3443 AN: 66638 Hom.: 560 Cov.: 0

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.: 0 AF XY: 0.0231 AC XY: 8348 AN XY: 360790

Gnomad4 AFR exome AF: 0.00654

Gnomad4 AMR exome AF: 0.0158

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.0521

Gnomad4 SAS exome AF: 0.0295

Gnomad4 FIN exome AF: 0.0273

Gnomad4 NFE exome AF: 0.0229

Gnomad4 OTH exome AF: 0.0240

GnomAD4 genome AF: 0.0516 AC: 3443 AN: 66676 Hom.: 560 Cov.: 0 AF XY: 0.0483 AC XY: 1425 AN XY: 29478

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0406

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0643

Gnomad4 OTH AF: 0.0653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs549270240; hg19: chr11-118955882;