11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr11-119085172-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
• rs549270240
• NM_000190.4:c.33+135_33+136insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_000190.4(HMBS):​c.33+135_33+136insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000030 (1 hom., cov: 0)
• Consequence: HMBS NM_000190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 0 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: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMBS	NM_000190.4	c.33+135_33+136insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 1 of 13	ENST00000652429.1	NP_000181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMBS	ENST00000652429.1	c.33+106_33+107insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 1 of 13		NM_000190.4	ENSP00000498786.1

Frequencies

GnomAD3 genomes AF: 0.0000300 AC: 2 AN: 66768 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000552

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000300 AC: 2 AN: 66768 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 29496

African (AFR) AF: 0.00 AC: 0 AN: 18368

American (AMR) AF: 0.00 AC: 0 AN: 4790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2142

East Asian (EAS) AF: 0.00 AC: 0 AN: 1402

South Asian (SAS) AF: 0.00 AC: 0 AN: 1312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 80

European-Non Finnish (NFE) AF: 0.0000552 AC: 2 AN: 36236

Other (OTH) AF: 0.00 AC: 0 AN: 852

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.50

Splicing

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

Other links and lift over

dbSNP: rs549270240; hg19: chr11-118955882;