rs11200638

Variant names:

• chr10-122461028-G-A
• rs11200638
• ENST00000648167.1:c.154+2319G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-122461028-G-A
• chr10-122461028-G-T

Variant summary

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

The ENST00000648167.1(HTRA1):​c.154+2319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,162 control chromosomes in the GnomAD database, including 4,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.23 (4399 hom., cov: 34)
• Consequence: HTRA1 ENST00000648167.1 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.125
• Publications: 295 publications found

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]

HTRA1 Gene-Disease associations (from GenCC):

• CARASIL syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• 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

HTRA1-AS1 (HGNC:58122):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648167.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTRA1	ENST00000648167.1		c.154+2319G>A		intron	N/A	ENSP00000498033.1	A0A3B3IU24
	HTRA1-AS1	ENST00000650300.1		n.356C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35620 AN: 152042 Hom.: 4389 Cov.: 34

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.234 AC: 35666 AN: 152162 Hom.: 4399 Cov.: 34 AF XY: 0.237 AC XY: 17634 AN XY: 74384

African (AFR) AF: 0.234 AC: 9738 AN: 41542

American (AMR) AF: 0.230 AC: 3521 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3468

East Asian (EAS) AF: 0.424 AC: 2176 AN: 5130

South Asian (SAS) AF: 0.316 AC: 1528 AN: 4832

European-Finnish (FIN) AF: 0.235 AC: 2487 AN: 10596

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14721 AN: 67968

Other (OTH) AF: 0.235 AC: 498 AN: 2116

Alfa AF: 0.222 Hom.: 4659

Bravo AF: 0.236

Asia WGS AF: 0.369 AC: 1277 AN: 3478

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Age related macular degeneration 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.87
PhyloP100		-0.13

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11200638;

hg19: chr10-124220544;

COSMIC: COSV64564929;