rs12267142

Positions:

• chr10-122488726-C-G
• chr10-122488726-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002775.5(HTRA1):​c.473-176C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 152,290 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.046 (235 hom., cov: 32)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-122488726-C-G is Benign according to our data. Variant chr10-122488726-C-G is described in ClinVar as [Benign]. Clinvar id is 1263788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5	c.473-176C>G		intron_variant		ENST00000368984.8	NP_002766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000368984.8	c.473-176C>G		intron_variant		1	NM_002775.5	ENSP00000357980	P1
HTRA1	ENST00000648167.1	c.155-176C>G		intron_variant				ENSP00000498033

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7057 AN: 152172 Hom.: 234 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0463 AC: 7056 AN: 152290 Hom.: 235 Cov.: 32 AF XY: 0.0440 AC XY: 3280 AN XY: 74468

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0364

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0224 Hom.: 12

Bravo AF: 0.0478

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.050
DANN	Benign	0.46

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: rs12267142; hg19: chr10-124248242;