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

Variant summary

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

The NM_000190.4(HMBS):c.33+130_33+135delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 790,702 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 0)

Exomes 𝑓: 0.020 ( 11 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 Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMBS	NM_000190.4 link	c.33+130_33+135delTTTTTT		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+112delTTTTTT		intron_variant	Intron 1 of 13		NM_000190.4	ENSP00000498786.1		P08397-1

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

139

AN:

66766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000544

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000418

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.0701

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000193

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0204

AC:

14734

AN:

723900

Hom.:

AF XY:

0.0207

AC XY:

7391

AN XY:

357690

show subpopulations

Gnomad4 AFR exome

AF:

0.0284

Gnomad4 AMR exome

AF:

0.0205

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.0380

Gnomad4 SAS exome

AF:

0.0350

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.0188

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.00210

AC:

140

AN:

66802

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

AN XY:

29536

show subpopulations

Gnomad4 AFR

AF:

0.000598

Gnomad4 AMR

AF:

0.000417

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0199

Gnomad4 SAS

AF:

0.0703

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000193

Gnomad4 OTH

AF:

0.00

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