Variant 10-122506984-C-T 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_002775.5(HTRA1):c.972+99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,084,920 control chromosomes in the GnomAD database, including 60,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7113 hom., cov: 32)

Exomes 𝑓: 0.33 ( 53371 hom. )

Consequence

HTRA1
NM_002775.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.133

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

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 10-122506984-C-T is Benign according to our data. Variant chr10-122506984-C-T is described in ClinVar as [Benign]. Clinvar id is 1233351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5 linkuse as main transcript	c.972+99C>T		intron_variant		ENST00000368984.8	NP_002766.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
HTRA1	ENST00000368984.8 linkuse as main transcript	c.972+99C>T	intron_variant	1	NM_002775.5	ENSP00000357980	P1
HTRA1	ENST00000420892.1 linkuse as main transcript	c.195+99C>T	intron_variant	2		ENSP00000412676
HTRA1	ENST00000648167.1 linkuse as main transcript	c.654+99C>T	intron_variant			ENSP00000498033

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44204

AN:

151800

Hom.:

7103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.332

AC:

309419

AN:

933002

Hom.:

53371

AF XY:

0.329

AC XY:

157766

AN XY:

479916

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.510

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.291

AC:

44234

AN:

151918

Hom.:

7113

Cov.:

AF XY:

0.293

AC XY:

21771

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.294

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.253

Hom.:

1090

Bravo

AF:

0.295

Asia WGS

AF:

0.357

AC:

1237

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.2

DANN

Benign

0.63

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