Variant 11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_000190.4(HMBS):c.33+124_33+135delTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 798,458 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 0.00097 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0049 ( 1 hom. )

Consequence

HMBS
NM_000190.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000973 (65/66808) while in subpopulation SAS AF= 0.00306 (4/1308). AF 95% confidence interval is 0.00104. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMBS	NM_000190.4 link	c.33+124_33+135delTTTTTTTTTTTT		intron_variant	Intron 1 of 13	ENST00000652429.1	NP_000181.2	P08397-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMBS	ENST00000652429.1 link	c.33+107_33+118delTTTTTTTTTTTT		intron_variant	Intron 1 of 13		NM_000190.4	ENSP00000498786.1		P08397-1

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

AN:

66772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00305

Gnomad FIN

AF:

0.00178

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000966

Gnomad OTH

AF:

0.00117

GnomAD4 exome

AF:

0.00491

AC:

3593

AN:

731650

Hom.:

AF XY:

0.00494

AC XY:

1789

AN XY:

361880

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.00399

Gnomad4 ASJ exome

AF:

0.00464

Gnomad4 EAS exome

AF:

0.00409

Gnomad4 SAS exome

AF:

0.00252

Gnomad4 FIN exome

AF:

0.00467

Gnomad4 NFE exome

AF:

0.00495

Gnomad4 OTH exome

AF:

0.00540

GnomAD4 genome

AF:

0.000973

AC:

AN:

66808

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

29540

show subpopulations

Gnomad4 AFR

AF:

0.000869

Gnomad4 AMR

AF:

0.00146

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00306

Gnomad4 FIN

AF:

0.00178

Gnomad4 NFE

AF:

0.000966

Gnomad4 OTH

AF:

0.00117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over