11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTT

Position:

• chr11-119085172-CTTTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000190.4(HMBS):​c.33+123_33+135del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (264 hom., cov: 0)
  • Exomes 𝑓: 0.095 (273 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMBS NM_000190.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.83

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-119085172-CTTTTTTTTTTTTT-C is Benign according to our data. Variant chr11-119085172-CTTTTTTTTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 445546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMBS	NM_000190.4	c.33+123_33+135del		intron_variant		ENST00000652429.1	NP_000181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMBS	ENST00000652429.1	c.33+123_33+135del		intron_variant			NM_000190.4	ENSP00000498786	P3

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 5983 AN: 66970 Hom.: 265 Cov.: 0

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0891

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.000712

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.119

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0947 AC: 69113 AN: 730024 Hom.: 273 AF XY: 0.0939 AC XY: 33907 AN XY: 360978

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.0384

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.00179

Gnomad4 SAS exome AF: 0.0651

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0919

GnomAD4 genome AF: 0.0892 AC: 5979 AN: 67004 Hom.: 264 Cov.: 0 AF XY: 0.0917 AC XY: 2719 AN XY: 29652

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.0751

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.000711

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.118

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 15, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs549270240; hg19: chr11-118955882;