rs8177796

Positions:

• chr9-113393148-G-A

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.113+299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 425,936 control chromosomes in the GnomAD database, including 1,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (522 hom., cov: 31)
  • Exomes 𝑓: 0.071 (862 hom.)
• Consequence: ALAD NM_000031.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

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=-0.83).
• BP6: Variant 9-113393148-G-A is Benign according to our data. Variant chr9-113393148-G-A is described in ClinVar as [Benign]. Clinvar id is 1237353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALAD	NM_000031.6	c.113+299C>T		intron_variant		ENST00000409155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALAD	ENST00000409155.8	c.113+299C>T		intron_variant		1	NM_000031.6	P1

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12159 AN: 152078 Hom.: 523 Cov.: 31

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0705 AC: 19310 AN: 273740 Hom.: 862 Cov.: 0 AF XY: 0.0666 AC XY: 9716 AN XY: 145972

Gnomad4 AFR exome AF: 0.0899

Gnomad4 AMR exome AF: 0.0376

Gnomad4 ASJ exome AF: 0.0683

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0311

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0836

Gnomad4 OTH exome AF: 0.0737

GnomAD4 genome AF: 0.0799 AC: 12167 AN: 152196 Hom.: 522 Cov.: 31 AF XY: 0.0802 AC XY: 5971 AN XY: 74416

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0791 Hom.: 475

Bravo AF: 0.0728

Asia WGS AF: 0.0160 AC: 55 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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.52

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: rs8177796; hg19: chr9-116155428;