11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_000190.4(HMBS):c.33+129_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 0.054 (672 hom., cov: 0)
  • Exomes 𝑓: 0.021 (1223 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 = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMBS	NM_000190.4	c.33+129_33+135dup		intron_variant		ENST00000652429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBS	ENST00000652429.1	c.33+129_33+135dup		intron_variant			NM_000190.4	P3

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 3610 AN: 66640 Hom.: 672 Cov.: 0

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.0326

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0932

Gnomad FIN AF: 0.00899

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0448

GnomAD4 exome AF: 0.0207 AC: 15124 AN: 730302 Hom.: 1223 Cov.: 0 AF XY: 0.0214 AC XY: 7730 AN XY: 361198

Gnomad4 AFR exome AF: 0.00463

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0159

Gnomad4 EAS exome AF: 0.0412

Gnomad4 SAS exome AF: 0.0331

Gnomad4 FIN exome AF: 0.0283

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.0541 AC: 3610 AN: 66678 Hom.: 672 Cov.: 0 AF XY: 0.0530 AC XY: 1561 AN XY: 29462

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.0381

Gnomad4 ASJ AF: 0.0763

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.00899

Gnomad4 NFE AF: 0.0682

Gnomad4 OTH AF: 0.0445

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;