10-122514155-C-T

Variant names:

Variant summary

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

The NM_002775.5(HTRA1):c.1275-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,605,236 control chromosomes in the GnomAD database, including 33,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.18 ( 2928 hom., cov: 31)

Exomes 𝑓: 0.20 ( 30930 hom. )

Consequence

HTRA1
NM_002775.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.246

Variant links:

Genes affected

HTRA1 (HGNC:9476): (HtrA serine peptidase 1) This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth. Variations in the promoter region of this gene are the cause of susceptibility to age-related macular degeneration type 7. [provided by RefSeq, Jul 2008]

HTRA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-122514155-C-T is Benign according to our data. Variant chr10-122514155-C-T is described in ClinVar as [Benign]. Clinvar id is 1259856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTRA1	NM_002775.5 link	c.1275-36C>T		intron_variant	Intron 8 of 8	ENST00000368984.8	NP_002766.1	Q92743

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTRA1	ENST00000368984.8 link	c.1275-36C>T	intron_variant	Intron 8 of 8	1	NM_002775.5	ENSP00000357980.3	Q92743
HTRA1	ENST00000648167.1 link	c.957-36C>T	intron_variant	Intron 8 of 8			ENSP00000498033.1	A0A3B3IU24
HTRA1	ENST00000420892.1 link	c.498-36C>T	intron_variant	Intron 5 of 5	2		ENSP00000412676.1	H0Y7G9

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28057

AN:

151920

Hom.:

2927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.221

AC:

55644

AN:

251330

Hom.:

7292

AF XY:

0.230

AC XY:

31266

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.432

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.195

AC:

283440

AN:

1453198

Hom.:

30930

Cov.:

AF XY:

0.201

AC XY:

145665

AN XY:

723596

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.185

AC:

28070

AN:

152038

Hom.:

2928

Cov.:

AF XY:

0.188

AC XY:

13962

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.211

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.417

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.177

Hom.:

1835

Bravo

AF:

0.189

Asia WGS

AF:

0.345

AC:

1204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31603204, 30859180) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CARASIL syndrome

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

-0.88

CADD

Benign

3.0

DANN

Benign

0.44

BranchPoint Hunter

0.0

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

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