11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000190.4(HMBS):c.33+122_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 0.00075 (9 hom., cov: 0)
  • Exomes 𝑓: 0.00084 (29 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd at 9 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMBS	NM_000190.4	c.33+122_33+135dup		intron_variant		ENST00000652429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBS	ENST00000652429.1	c.33+122_33+135dup		intron_variant			NM_000190.4	P3

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 50 AN: 66768 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.000109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00140

Gnomad EAS AF: 0.00428

Gnomad SAS AF: 0.00305

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000938

Gnomad OTH AF: 0.00117

GnomAD4 exome AF: 0.000845 AC: 619 AN: 732704 Hom.: 29 Cov.: 0 AF XY: 0.000891 AC XY: 323 AN XY: 362418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000677

Gnomad4 ASJ exome AF: 0.000675

Gnomad4 EAS exome AF: 0.00217

Gnomad4 SAS exome AF: 0.00168

Gnomad4 FIN exome AF: 0.00167

Gnomad4 NFE exome AF: 0.000782

Gnomad4 OTH exome AF: 0.000724

GnomAD4 genome AF: 0.000748 AC: 50 AN: 66804 Hom.: 9 Cov.: 0 AF XY: 0.000846 AC XY: 25 AN XY: 29540

Gnomad4 AFR AF: 0.000109

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00140

Gnomad4 EAS AF: 0.00427

Gnomad4 SAS AF: 0.00306

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000938

Gnomad4 OTH AF: 0.00117

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;