rs8177812

chr9-113389247-G-Achr9-113389247-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000031.6(ALAD):c.802-141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,405,648 control chromosomes in the GnomAD database, including 15,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1732 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13360 hom.)
• Consequence: ALAD NM_000031.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00600

Genes affected

ALAD (HGNC:395): (aminolevulinate dehydratase) The ALAD enzyme is composed of 8 identical subunits and catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is essential for enzymatic activity. ALAD enzymatic activity is inhibited by lead and a defect in the ALAD structural gene can cause increased sensitivity to lead poisoning and acute hepatic porphyria. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-113389247-G-A is Benign according to our data. Variant chr9-113389247-G-A is described in ClinVar as [Benign]. Clinvar id is 1267385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALAD	NM_000031.6	c.802-141C>T		intron_variant		ENST00000409155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALAD	ENST00000409155.8	c.802-141C>T		intron_variant		1	NM_000031.6	P1
ALAD	ENST00000482847.5	n.1075-141C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21438 AN: 152044 Hom.: 1733 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.138 AC: 173262 AN: 1253486 Hom.: 13360 AF XY: 0.142 AC XY: 88527 AN XY: 623392

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.141 AC: 21439 AN: 152162 Hom.: 1732 Cov.: 32 AF XY: 0.143 AC XY: 10665 AN XY: 74388

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.142

Alfa AF: 0.134 Hom.: 1982

Bravo AF: 0.144

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.86
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8177812; hg19: chr9-116151527; COSMIC: COSV52961248; COSMIC: COSV52961248;