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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000190.4(HMBS):c.33+122_33+135dupTTTTTTTTTTTTTT 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 0.00075 ( 9 hom., cov: 0)

Exomes 𝑓: 0.00084 ( 29 hom. )

Consequence

HMBS
NM_000190.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.497

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.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000748 (50/66804) while in subpopulation EAS AF= 0.00427 (6/1404). AF 95% confidence interval is 0.00186. There are 9 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMBS	NM_000190.4 link	c.33+122_33+135dupTTTTTTTTTTTTTT		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+106_33+107insTTTTTTTTTTTTTT		intron_variant	Intron 1 of 13		NM_000190.4	ENSP00000498786.1		P08397-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

AN:

66768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00140

Gnomad EAS

AF:

0.00428

Gnomad SAS

AF:

0.00305

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000938

Gnomad OTH

AF:

0.00117

GnomAD4 exome

AF:

0.000845

AC:

619

AN:

732704

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

323

AN XY:

362418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000677

Gnomad4 ASJ exome

AF:

0.000675

Gnomad4 EAS exome

AF:

0.00217

Gnomad4 SAS exome

AF:

0.00168

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.000782

Gnomad4 OTH exome

AF:

0.000724

GnomAD4 genome

AF:

0.000748

AC:

AN:

66804

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

29540

show subpopulations

Gnomad4 AFR

AF:

0.000109

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00140

Gnomad4 EAS

AF:

0.00427

Gnomad4 SAS

AF:

0.00306

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000938

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