chr11-119084878-CG-C

Variant names:

• chr11-119084878-CG-C
• ENST00000933407.1:c.-154delG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000933407.1(HMBS):​c.-154delG variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HMBS ENST00000933407.1 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.56
• Publications: 1 publications found

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]

HMBS Gene-Disease associations (from GenCC):

• acute intermittent porphyria

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-119084878-CG-C is Pathogenic according to our data. Variant chr11-119084878-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1481.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000933407.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMBS	NM_000190.4	MANE Select	c.-155delG		upstream_gene	N/A	NP_000181.2
	HMBS	NM_001425056.1		c.-155delG		upstream_gene	N/A	NP_001411985.1
	HMBS	NM_001425057.1		c.-155delG		upstream_gene	N/A	NP_001411986.1	A0A3F2YNY7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMBS	ENST00000933407.1		c.-154delG		5_prime_UTR	Exon 1 of 13	ENSP00000603466.1
	HMBS	ENST00000933409.1		c.-154delG		5_prime_UTR	Exon 1 of 12	ENSP00000603468.1
	HMBS	ENST00000959927.1		c.-154delG		5_prime_UTR	Exon 1 of 12	ENSP00000629986.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Porphyria, acute intermittent, nonerythroid variant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-118955588;