rs604630

Variant names:

• chr11-65882303-A-G
• rs604630
• NM_001335.4:c.415A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-65882303-A-G
• chr11-65882303-A-T

Variant summary

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

The NM_001335.4(CTSW):​c.415A>G​(p.Ser139Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,614,124 control chromosomes in the GnomAD database, including 788,721 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.94 (67445 hom., cov: 32)
  • Exomes 𝑓: 0.99 (721276 hom.)
• Consequence: CTSW NM_001335.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 27 publications found

Genes affected

CTSW (HGNC:2546): (cathepsin W) The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.6164156E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001335.4. 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
	CTSW	NM_001335.4	MANE Select	c.415A>G	p.Ser139Gly	missense	Exon 4 of 10	NP_001326.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSW	ENST00000307886.8	TSL:1 MANE Select	c.415A>G	p.Ser139Gly	missense	Exon 4 of 10	ENSP00000311300.3
	CTSW	ENST00000680443.1		c.505A>G	p.Ser169Gly	missense	Exon 4 of 10	ENSP00000505179.1
	CTSW	ENST00000894913.1		c.415A>G	p.Ser139Gly	missense	Exon 4 of 10	ENSP00000564972.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142446 AN: 152142 Hom.: 67405 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.948

GnomAD2 exomes AF: 0.983 AC: 247185 AN: 251410 AF XY: 0.988

Gnomad AFR exome AF: 0.781

Gnomad AMR exome AF: 0.988

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.991

GnomAD4 exome AF: 0.993 AC: 1451250 AN: 1461864 Hom.: 721276 Cov.: 67 AF XY: 0.994 AC XY: 722679 AN XY: 727232

African (AFR) AF: 0.772 AC: 25835 AN: 33480

American (AMR) AF: 0.986 AC: 44112 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 26102 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39699 AN: 39700

South Asian (SAS) AF: 0.999 AC: 86206 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53376 AN: 53398

Middle Eastern (MID) AF: 0.984 AC: 5678 AN: 5768

European-Non Finnish (NFE) AF: 0.999 AC: 1110893 AN: 1112006

Other (OTH) AF: 0.983 AC: 59349 AN: 60394

GnomAD4 genome AF: 0.936 AC: 142544 AN: 152260 Hom.: 67445 Cov.: 32 AF XY: 0.940 AC XY: 69955 AN XY: 74452

African (AFR) AF: 0.783 AC: 32503 AN: 41506

American (AMR) AF: 0.969 AC: 14820 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3467 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5167 AN: 5168

South Asian (SAS) AF: 0.999 AC: 4827 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10630

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67938 AN: 68034

Other (OTH) AF: 0.949 AC: 2008 AN: 2116

Alfa AF: 0.977 Hom.: 175594

Bravo AF: 0.929

TwinsUK AF: 0.999 AC: 3704

ALSPAC AF: 0.999 AC: 3849

ESP6500AA AF: 0.805 AC: 3544

ESP6500EA AF: 0.999 AC: 8585

ExAC AF: 0.980 AC: 118960

Asia WGS AF: 0.988 AC: 3434 AN: 3478

EpiCase AF: 0.998

EpiControl AF: 0.998

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.021
DANN	Benign	0.34
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-0.91
PrimateAI	Benign	0.31	T
PROVEAN	Benign	3.1	N
REVEL	Benign	0.010
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.056
ClinPred		0.0018	T
GERP RS		-1.7
Varity_R		0.030
gMVP		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs604630; hg19: chr11-65649774; COSMIC: COSV107332612; COSMIC: COSV107332612;