chr10-122461028-G-T

Variant names:

• chr10-122461028-G-T
• rs11200638
• ENST00000650300.1:n.356C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000650300.1(ENSG00000285955):​n.356C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: ENSG00000285955 ENST00000650300.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 294 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTRA1-AS1	XR_946382.3	n.378C>A		non_coding_transcript_exon_variant	Exon 1 of 3
HTRA1-AS1	XR_946383.3	n.356C>A		non_coding_transcript_exon_variant	Exon 1 of 4
HTRA1-AS1	XR_946384.3	n.356C>A		non_coding_transcript_exon_variant	Exon 1 of 4
HTRA1-AS1	XR_946385.3	n.356C>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.356C>A		non_coding_transcript_exon_variant	Exon 1 of 3
HTRA1	ENST00000648167.1	c.154+2319G>T		intron_variant	Intron 1 of 8			ENSP00000498033.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 4659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.58
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs11200638; hg19: chr10-124220544;