ENST00000619238.2:n.-222A>C

Variant names:

• chr20-23425882-A-C
• rs6076072
• ENST00000619238.2:n.-222A>C

Variant summary

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

The ENST00000619238.2(CSTL1):​n.-222A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 152,194 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.080 (650 hom., cov: 33)
• Consequence: CSTL1 ENST00000619238.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 9 publications found

Genes affected

CSTL1 (HGNC:15958): (cystatin like 1) The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located at the telomeric end of the cystatin locus and encodes a type 2 cystatin-like protein. The specific function of this protein has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTL1	ENST00000619238.2	n.-222A>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12230 AN: 152076 Hom.: 648 Cov.: 33

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0685

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0804 AC: 12233 AN: 152194 Hom.: 650 Cov.: 33 AF XY: 0.0805 AC XY: 5988 AN XY: 74390

African (AFR) AF: 0.0211 AC: 877 AN: 41546

American (AMR) AF: 0.134 AC: 2049 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5188

South Asian (SAS) AF: 0.0686 AC: 331 AN: 4826

European-Finnish (FIN) AF: 0.0982 AC: 1038 AN: 10566

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7471 AN: 68008

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0957 Hom.: 812

Bravo AF: 0.0814

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.69
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs6076072; hg19: chr20-23406519;