chr9-113391819-C-T

Variant names:

• chr9-113391819-C-T
• rs8177800
• NM_000031.6:c.165-196G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000031.6(ALAD):​c.165-196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 152,246 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.055 (284 hom., cov: 32)
• Consequence: ALAD NM_000031.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.834
• Publications: 4 publications found

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]

ALAD Gene-Disease associations (from GenCC):

• porphyria due to ALA dehydratase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-113391819-C-T is Benign according to our data. Variant chr9-113391819-C-T is described in ClinVar as Benign. ClinVar VariationId is 1242974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALAD	NM_000031.6	c.165-196G>A		intron_variant	Intron 3 of 11	ENST00000409155.8	NP_000022.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALAD	ENST00000409155.8	c.165-196G>A		intron_variant	Intron 3 of 11	1	NM_000031.6	ENSP00000386284.3

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8368 AN: 152128 Hom.: 283 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0790

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0666

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0550 AC: 8375 AN: 152246 Hom.: 284 Cov.: 32 AF XY: 0.0541 AC XY: 4030 AN XY: 74456

African (AFR) AF: 0.0124 AC: 515 AN: 41544

American (AMR) AF: 0.0533 AC: 815 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0296 AC: 143 AN: 4830

European-Finnish (FIN) AF: 0.0790 AC: 838 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5460 AN: 67996

Other (OTH) AF: 0.0668 AC: 141 AN: 2110

Alfa AF: 0.0671 Hom.: 234

Bravo AF: 0.0529

Asia WGS AF: 0.0170 AC: 61 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8177800; hg19: chr9-116154099;