chr9-113396819-C-T

Position:

• chr9-113396819-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000409155.8(ALAD):​c.-75-3185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,982 control chromosomes in the GnomAD database, including 2,481 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2465 hom., cov: 31)
  • Exomes 𝑓: 0.18 (16 hom.)
• Consequence: ALAD ENST00000409155.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALAD	NM_000031.6	c.-75-3185G>A		intron_variant		ENST00000409155.8	NP_000022.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALAD	ENST00000409155.8	c.-75-3185G>A		intron_variant		1	NM_000031.6	ENSP00000386284	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26467 AN: 151846 Hom.: 2453 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.178 AC: 181 AN: 1018 Hom.: 16 Cov.: 0 AF XY: 0.179 AC XY: 117 AN XY: 654

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.174 AC: 26507 AN: 151964 Hom.: 2465 Cov.: 31 AF XY: 0.174 AC XY: 12965 AN XY: 74298

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0252

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.164

Alfa AF: 0.175 Hom.: 1306

Bravo AF: 0.165

Asia WGS AF: 0.117 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.62

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: rs2792818; hg19: chr9-116159099;