10-122459759-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000650300.1(ENSG00000285955):n.588G>C 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 0.237 in 151,962 control chromosomes in the GnomAD database, including 4,464 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 0.24 (4464 hom., cov: 31)
• Consequence: ENST00000650300.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

Genes affected

(HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105378525	XR_946382.3	n.610G>C		non_coding_transcript_exon_variant	2/3
LOC105378525	XR_946383.3	n.588G>C		non_coding_transcript_exon_variant	2/4
LOC105378525	XR_946384.3	n.588G>C		non_coding_transcript_exon_variant	2/4
LOC105378525	XR_946385.3	n.588G>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000650300.1	n.588G>C		non_coding_transcript_exon_variant	2/3
HTRA1	ENST00000648167.1	c.154+1050C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35892 AN: 151844 Hom.: 4456 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.237 AC: 35941 AN: 151962 Hom.: 4464 Cov.: 31 AF XY: 0.239 AC XY: 17777 AN XY: 74280

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.236

Alfa AF: 0.149 Hom.: 298

Bravo AF: 0.239

Asia WGS AF: 0.371 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.84
Dann	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3793917; hg19: chr10-124219275;