rs551607350

Variant names:

• chr11-1753363-C-A
• rs551607350
• NM_001909.5:c.*140G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1753363-C-A
• chr11-1753363-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001909.5(CTSD):​c.*140G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,007,902 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (7 hom.)
• Consequence: CTSD NM_001909.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.904
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-1753363-C-A is Benign according to our data. Variant chr11-1753363-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 303829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000223 (34/152286) while in subpopulation SAS AF = 0.00704 (34/4830). AF 95% confidence interval is 0.00518. There are 1 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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.*140G>T		3_prime_UTR	Exon 9 of 9	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.*140G>T		3_prime_UTR	Exon 9 of 9	ENSP00000236671.2	P07339
	ENSG00000250644	ENST00000636615.1	TSL:5	c.1071+440G>T		intron	N/A	ENSP00000490014.1	A0A1B0GU92
	CTSD	ENST00000962446.1		c.*140G>T		3_prime_UTR	Exon 10 of 10	ENSP00000632505.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152168 Hom.: 1 Cov.: 33

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: 0.00724

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000386 AC: 330 AN: 855616 Hom.: 7 Cov.: 12 AF XY: 0.000540 AC XY: 241 AN XY: 446112

African (AFR) AF: 0.00 AC: 0 AN: 21688

American (AMR) AF: 0.00 AC: 0 AN: 39720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21722

East Asian (EAS) AF: 0.00 AC: 0 AN: 36052

South Asian (SAS) AF: 0.00435 AC: 314 AN: 72150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41882

Middle Eastern (MID) AF: 0.000255 AC: 1 AN: 3916

European-Non Finnish (NFE) AF: 0.00000173 AC: 1 AN: 578100

Other (OTH) AF: 0.000347 AC: 14 AN: 40386

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152286 Hom.: 1 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74458

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Neuronal ceroid lipofuscinosis 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.78
PhyloP100		-0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs551607350; hg19: chr11-1774593;