Variant 2-42770474-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012205.3(HAAO):c.440+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,508,526 control chromosomes in the GnomAD database, including 113,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10294 hom., cov: 31)

Exomes 𝑓: 0.38 ( 102710 hom. )

Consequence

HAAO
NM_012205.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0250

Variant links:

Genes affected

HAAO (HGNC:4796): (3-hydroxyanthranilate 3,4-dioxygenase) 3-Hydroxyanthranilate 3,4-dioxygenase is a monomeric cytosolic protein belonging to the family of intramolecular dioxygenases containing nonheme ferrous iron. It is widely distributed in peripheral organs, such as liver and kidney, and is also present in low amounts in the central nervous system. HAAO catalyzes the synthesis of quinolinic acid (QUIN) from 3-hydroxyanthranilic acid. QUIN is an excitotoxin whose toxicity is mediated by its ability to activate glutamate N-methyl-D-aspartate receptors. Increased cerebral levels of QUIN may participate in the pathogenesis of neurologic and inflammatory disorders. HAAO has been suggested to play a role in disorders associated with altered tissue levels of QUIN. [provided by RefSeq, Jul 2008]

HAAO links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-42770474-G-A is Benign according to our data. Variant chr2-42770474-G-A is described in ClinVar as [Benign]. Clinvar id is 1285320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
HAAO	NM_012205.3 link	c.440+19C>T	intron_variant	ENST00000294973.11	NP_036337.2	P46952-1
HAAO	XM_011532729.4 link	c.351-288C>T	intron_variant		XP_011531031.1
HAAO	XM_011532730.4 link	c.338+19C>T	intron_variant		XP_011531032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAAO	ENST00000294973.11 link	c.440+19C>T		intron_variant		1	NM_012205.3	ENSP00000294973.6		P46952-1

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54472

AN:

151926

Hom.:

10292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.379

GnomAD3 exomes

AF:

0.401

AC:

58149

AN:

145054

Hom.:

12334

AF XY:

0.406

AC XY:

30795

AN XY:

75834

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.634

Gnomad SAS exome

AF:

0.438

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.384

AC:

520992

AN:

1356482

Hom.:

102710

Cov.:

AF XY:

0.386

AC XY:

258514

AN XY:

669992

show subpopulations

Gnomad4 AFR exome

AF:

0.263

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.432

Gnomad4 EAS exome

AF:

0.654

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.384

GnomAD4 genome

AF:

0.358

AC:

54477

AN:

152044

Hom.:

10294

Cov.:

AF XY:

0.361

AC XY:

26867

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.341

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.641

Gnomad4 SAS

AF:

0.444

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.378

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.381

Hom.:

13692

Bravo

AF:

0.347

Asia WGS

AF:

0.519

AC:

1803

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Vertebral, cardiac, renal, and limb defects syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.4

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over