dbSNP rs3918270: SLC12A5-AS1:n.669-1912C>T (chr20-46016700-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000535913.2(SLC12A5-AS1):n.669-1912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 348,140 control chromosomes in the GnomAD database, including 5,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1923 hom., cov: 30)

Exomes 𝑓: 0.16 ( 3194 hom. )

Consequence

SLC12A5-AS1
ENST00000535913.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34

Variant links:

Genes affected

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

SLC12A5-AS1 links:

MMP9 (HGNC:7176): (matrix metallopeptidase 9) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

MMP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 20-46016700-G-A is Benign according to our data. Variant chr20-46016700-G-A is described in ClinVar as [Benign]. Clinvar id is 1260772.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A5-AS1	NR_147699.1 link	n.669-1912C>T		intron_variant	Intron 2 of 2
MMP9	NM_004994.3 link	c.*332G>A		downstream_gene_variant		ENST00000372330.3	NP_004985.2	P14780

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A5-AS1	ENST00000535913.2 link	n.669-1912C>T		intron_variant	Intron 2 of 2	2
MMP9	ENST00000372330.3 link	c.*332G>A		downstream_gene_variant		1	NM_004994.3	ENSP00000361405.3		P14780

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23435

AN:

151274

Hom.:

1925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0933

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.135

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.161

AC:

31671

AN:

196754

Hom.:

3194

AF XY:

0.174

AC XY:

18727

AN XY:

107662

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.0740

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.155

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.155

AC:

23449

AN:

151386

Hom.:

1923

Cov.:

AF XY:

0.157

AC XY:

11577

AN XY:

73938

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.0930

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.160

Hom.:

278

Bravo

AF:

0.147

Asia WGS

AF:

0.206

AC:

713

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.99

DANN

Benign

0.51

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over