chr10-122461681-CGCT-C

Variant names:

• chr10-122461681-CGCT-C
• rs746547640
• NM_002775.5:c.46_48delCTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_Supporting BP6 BS1

The NM_002775.5(HTRA1):​c.46_48delCTG​(p.Leu16del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,263,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: HTRA1 NM_002775.5 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892

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 Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_002775.5. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-122461681-CGCT-C is Benign according to our data. Variant chr10-122461681-CGCT-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00352 (3933/1115780) while in subpopulation AMR AF= 0.0101 (207/20418). AF 95% confidence interval is 0.00907. There are 0 homozygotes in gnomad4_exome. There are 2089 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTRA1	NM_002775.5	c.46_48delCTG	p.Leu16del	conservative_inframe_deletion	Exon 1 of 9	ENST00000368984.8	NP_002766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000368984.8	c.46_48delCTG	p.Leu16del	conservative_inframe_deletion	Exon 1 of 9	1	NM_002775.5	ENSP00000357980.3
HTRA1	ENST00000648167.1	c.154+2989_154+2991delCTG		intron_variant	Intron 1 of 8			ENSP00000498033.1

Frequencies

GnomAD3 genomes AF: 0.0000543 AC: 8 AN: 147438 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000224

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000907

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00352 AC: 3933 AN: 1115780 Hom.: 0 AF XY: 0.00381 AC XY: 2089 AN XY: 547922

Gnomad4 AFR exome AF: 0.00310

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.00606

Gnomad4 EAS exome AF: 0.00887

Gnomad4 SAS exome AF: 0.00971

Gnomad4 FIN exome AF: 0.00982

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.00542

GnomAD4 genome AF: 0.0000543 AC: 8 AN: 147438 Hom.: 0 Cov.: 32 AF XY: 0.0000558 AC XY: 4 AN XY: 71716

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000224

Gnomad4 NFE AF: 0.0000907

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs746547640; hg19: chr10-124221197;