11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTT

Position:

• chr11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000190.4(HMBS):​c.33+120_33+135del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 799,150 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00099 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (0 hom.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMBS	NM_000190.4	c.33+120_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+120_33+135del		intron_variant			NM_000190.4	ENSP00000498786	P3

Frequencies

GnomAD3 genomes AF: 0.000988 AC: 66 AN: 66768 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000690

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00119 AC: 875 AN: 732346 Hom.: 0 AF XY: 0.00122 AC XY: 441 AN XY: 362216

Gnomad4 AFR exome AF: 0.00201

Gnomad4 AMR exome AF: 0.000931

Gnomad4 ASJ exome AF: 0.000773

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.00141

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.000988 AC: 66 AN: 66804 Hom.: 1 Cov.: 0 AF XY: 0.00115 AC XY: 34 AN XY: 29540

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.000209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000690

Gnomad4 OTH AF: 0.00

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;