rs55928386

Variant names:

• chr10-122461151-C-T
• rs55928386
• ENST00000650300.1:n.233G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000650300.1(ENSG00000285955):​n.233G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,204 control chromosomes in the GnomAD database, including 1,811 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1811 hom., cov: 34)
• Consequence: ENSG00000285955 ENST00000650300.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 9 publications found

Genes affected

ENSG00000285955 (HGNC:58122):

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 Gene-Disease associations (from GenCC):

• CARASIL syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• genetic cerebral small vessel disease

  Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
• HTRA1-related autosomal dominant cerebral small vessel disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTRA1-AS1	XR_946382.3	n.255G>A		non_coding_transcript_exon_variant	Exon 1 of 3
HTRA1-AS1	XR_946383.3	n.233G>A		non_coding_transcript_exon_variant	Exon 1 of 4
HTRA1-AS1	XR_946384.3	n.233G>A		non_coding_transcript_exon_variant	Exon 1 of 4
HTRA1-AS1	XR_946385.3	n.233G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285955	ENST00000650300.1	n.233G>A		non_coding_transcript_exon_variant	Exon 1 of 3
HTRA1	ENST00000648167.1	c.154+2442C>T		intron_variant	Intron 1 of 8			ENSP00000498033.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19950 AN: 152096 Hom.: 1807 Cov.: 34

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.131 AC: 19969 AN: 152204 Hom.: 1811 Cov.: 34 AF XY: 0.128 AC XY: 9549 AN XY: 74418

African (AFR) AF: 0.249 AC: 10342 AN: 41556

American (AMR) AF: 0.0875 AC: 1338 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.0744 AC: 383 AN: 5150

South Asian (SAS) AF: 0.0771 AC: 372 AN: 4828

European-Finnish (FIN) AF: 0.0537 AC: 570 AN: 10612

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0958 AC: 6514 AN: 67970

Other (OTH) AF: 0.120 AC: 253 AN: 2114

Alfa AF: 0.110 Hom.: 154

Bravo AF: 0.139

Asia WGS AF: 0.100 AC: 348 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.85
PhyloP100		-2.8
PromoterAI		0.00060	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs55928386; hg19: chr10-124220667;