11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000190.4(HMBS):c.33+131_33+135del 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 0.0013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.040 (24 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMBS NM_000190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMBS	NM_000190.4	c.33+131_33+135del		intron_variant		ENST00000652429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBS	ENST00000652429.1	c.33+131_33+135del		intron_variant			NM_000190.4	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 87 AN: 66760 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000418

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00929

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000248

Gnomad OTH AF: 0.00235

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0402 AC: 28890 AN: 719240 Hom.: 24 AF XY: 0.0395 AC XY: 14032 AN XY: 355310

Gnomad4 AFR exome AF: 0.0588

Gnomad4 AMR exome AF: 0.0380

Gnomad4 ASJ exome AF: 0.0389

Gnomad4 EAS exome AF: 0.0394

Gnomad4 SAS exome AF: 0.0339

Gnomad4 FIN exome AF: 0.0231

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00130 AC: 87 AN: 66796 Hom.: 0 Cov.: 0 AF XY: 0.00132 AC XY: 39 AN XY: 29536

Gnomad4 AFR AF: 0.00315

Gnomad4 AMR AF: 0.000417

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00927

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000248

Gnomad4 OTH AF: 0.00233

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;