rs7126177

Variant names:

• chr11-1759104-G-A
• rs7126177
• NM_001909.5:c.353-17C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1759104-G-A
• chr11-1759104-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001909.5(CTSD):​c.353-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,576,698 control chromosomes in the GnomAD database, including 1,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (953 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (847 hom.)
• Consequence: CTSD NM_001909.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.135
• Publications: 1 publications found

Genes affected

CTSD (HGNC:2529): (cathepsin D) This gene encodes a member of the A1 family of peptidases. The encoded preproprotein is proteolytically processed to generate multiple protein products. These products include the cathepsin D light and heavy chains, which heterodimerize to form the mature enzyme. This enzyme exhibits pepsin-like activity and plays a role in protein turnover and in the proteolytic activation of hormones and growth factors. Mutations in this gene play a causal role in neuronal ceroid lipofuscinosis-10 and may be involved in the pathogenesis of several other diseases, including breast cancer and possibly Alzheimer's disease. [provided by RefSeq, Nov 2015]

CTSD Gene-Disease associations (from GenCC):

• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuronal ceroid lipofuscinosis 10

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P

ENSG00000250644 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-1759104-G-A is Benign according to our data. Variant chr11-1759104-G-A is described in ClinVar as Benign. ClinVar VariationId is 137054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001909.5. 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
	CTSD	NM_001909.5	MANE Select	c.353-17C>T		intron	N/A	NP_001900.1	P07339

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSD	ENST00000236671.7	TSL:1 MANE Select	c.353-17C>T		intron	N/A	ENSP00000236671.2	P07339
	ENSG00000250644	ENST00000636615.1	TSL:5	c.353-17C>T		intron	N/A	ENSP00000490014.1	A0A1B0GU92
	ENSG00000250644	ENST00000636397.1	TSL:5	c.353-17C>T		intron	N/A	ENSP00000489910.1	A0A1B0GU03

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9391 AN: 152174 Hom.: 951 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0425

GnomAD2 exomes AF: 0.0156 AC: 3911 AN: 250584 AF XY: 0.0116

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.00919

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000558

Gnomad OTH exome AF: 0.00654

GnomAD4 exome AF: 0.00621 AC: 8844 AN: 1424406 Hom.: 847 Cov.: 27 AF XY: 0.00530 AC XY: 3769 AN XY: 710808

African (AFR) AF: 0.216 AC: 7100 AN: 32802

American (AMR) AF: 0.0111 AC: 495 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.000269 AC: 23 AN: 85502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00595 AC: 34 AN: 5710

European-Non Finnish (NFE) AF: 0.000357 AC: 385 AN: 1077950

Other (OTH) AF: 0.0137 AC: 807 AN: 59116

GnomAD4 genome AF: 0.0617 AC: 9399 AN: 152292 Hom.: 953 Cov.: 33 AF XY: 0.0601 AC XY: 4473 AN XY: 74476

African (AFR) AF: 0.215 AC: 8922 AN: 41536

American (AMR) AF: 0.0210 AC: 322 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68022

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.00284 Hom.: 3

Bravo AF: 0.0699

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Neuronal ceroid lipofuscinosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.67
PhyloP100		-0.14
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7126177; hg19: chr11-1780334;