Variant rs2241028 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_013247.5(HTRA2):c.1046-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,612,272 control chromosomes in the GnomAD database, including 3,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 267 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3413 hom. )

Consequence

HTRA2
NM_013247.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0200

Variant links:

Genes affected

HTRA2 (HGNC:14348): (HtrA serine peptidase 2) This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

HTRA2 links:

HTRA2 (HGNC:):

HTRA2 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=-0.87).

BP6

Variant 2-74531807-G-A is Benign according to our data. Variant chr2-74531807-G-A is described in ClinVar as [Benign]. Clinvar id is 671226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA2	NM_013247.5 linkuse as main transcript	c.1046-49G>A		intron_variant		ENST00000258080.8	NP_037379.1	O43464-1A0A384MDW9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTRA2	ENST00000258080.8 linkuse as main transcript	c.1046-49G>A		intron_variant		1	NM_013247.5	ENSP00000258080.3		O43464-1

Frequencies

GnomAD3 genomes

AF:

0.0507

AC:

7710

AN:

152112

Hom.:

267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.0883

Gnomad FIN

AF:

0.0760

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0567

Gnomad OTH

AF:

0.0473

GnomAD3 exomes

AF:

0.0613

AC:

15377

AN:

250944

Hom.:

655

AF XY:

0.0639

AC XY:

8667

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.0834

Gnomad FIN exome

AF:

0.0759

Gnomad NFE exome

AF:

0.0561

Gnomad OTH exome

AF:

0.0531

GnomAD4 exome

AF:

0.0623

AC:

91032

AN:

1460042

Hom.:

3413

Cov.:

AF XY:

0.0633

AC XY:

45994

AN XY:

726370

show subpopulations

Gnomad4 AFR exome

AF:

0.0160

Gnomad4 AMR exome

AF:

0.0312

Gnomad4 ASJ exome

AF:

0.0230

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.0846

Gnomad4 FIN exome

AF:

0.0764

Gnomad4 NFE exome

AF:

0.0588

Gnomad4 OTH exome

AF:

0.0621

GnomAD4 genome

AF:

0.0506

AC:

7707

AN:

152230

Hom.:

267

Cov.:

AF XY:

0.0528

AC XY:

3932

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.0439

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.0884

Gnomad4 FIN

AF:

0.0760

Gnomad4 NFE

AF:

0.0567

Gnomad4 OTH

AF:

0.0468

Alfa

AF:

0.0552

Hom.:

333

Bravo

AF:

0.0469

Asia WGS

AF:

0.120

AC:

415

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.8

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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