10-122489719-C-T

Position:

• chr10-122489719-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002775.5(HTRA1):​c.777+93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,198,730 control chromosomes in the GnomAD database, including 15,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1992 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13111 hom.)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.778

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-122489719-C-T is Benign according to our data. Variant chr10-122489719-C-T is described in ClinVar as [Benign]. Clinvar id is 1273644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTRA1	NM_002775.5	c.777+93C>T		intron_variant		ENST00000368984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTRA1	ENST00000368984.8	c.777+93C>T		intron_variant		1	NM_002775.5	P1
HTRA1	ENST00000648167.1	c.459+93C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22607 AN: 151574 Hom.: 1985 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.139 AC: 145415 AN: 1047038 Hom.: 13111 AF XY: 0.147 AC XY: 78026 AN XY: 531594

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.149 AC: 22651 AN: 151692 Hom.: 1992 Cov.: 32 AF XY: 0.154 AC XY: 11409 AN XY: 74114

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.162

Alfa AF: 0.121 Hom.: 1640

Bravo AF: 0.154

Asia WGS AF: 0.320 AC: 1117 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
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	-0.86
CADD	Benign	2.5
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

Other links and lift over

dbSNP: rs2239586; hg19: chr10-124249235; COSMIC: COSV64564398;