11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTT

Position:

• chr11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_000190.4(HMBS):​c.33+132_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 0.034 (57 hom., cov: 0)
  • Exomes 𝑓: 0.090 (348 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	Protein	UniProt
HMBS	NM_000190.4	c.33+132_33+135del		intron_variant		ENST00000652429.1	NP_000181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMBS	ENST00000652429.1	c.33+132_33+135del		intron_variant			NM_000190.4	ENSP00000498786	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2262 AN: 66604 Hom.: 56 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.000467

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.00381

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0270

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0898 AC: 63958 AN: 712200 Hom.: 348 AF XY: 0.0889 AC XY: 31232 AN XY: 351418

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0735

Gnomad4 ASJ exome AF: 0.0727

Gnomad4 EAS exome AF: 0.0639

Gnomad4 SAS exome AF: 0.0699

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.0925

Gnomad4 OTH exome AF: 0.0874

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0340 AC: 2265 AN: 66644 Hom.: 57 Cov.: 0 AF XY: 0.0361 AC XY: 1063 AN XY: 29458

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.000467

Gnomad4 EAS AF: 0.0256

Gnomad4 SAS AF: 0.00382

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.0268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs549270240; hg19: chr11-118955882;