5-128186851-C-T

Position:

• chr5-128186851-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001046.3(SLC12A2):​c.*220C>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 0.222 in 401,780 control chromosomes in the GnomAD database, including 10,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3590 hom., cov: 32)
  • Exomes 𝑓: 0.23 (6804 hom.)
• Consequence: SLC12A2 NM_001046.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.257

Genes affected

SLC12A2 (HGNC:10911): (solute carrier family 12 member 2) The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-128186851-C-T is Benign according to our data. Variant chr5-128186851-C-T is described in ClinVar as [Benign]. Clinvar id is 1294739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A2	NM_001046.3	c.*220C>T		3_prime_UTR_variant	27/27	ENST00000262461.7
SLC12A2	NM_001256461.2	c.*220C>T		3_prime_UTR_variant	26/26
SLC12A2	NR_046207.2	n.4114C>T		non_coding_transcript_exon_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A2	ENST00000262461.7	c.*220C>T		3_prime_UTR_variant	27/27	1	NM_001046.3	P4
SLC12A2	ENST00000343225.4	c.*220C>T		3_prime_UTR_variant	26/26	1		A2
SLC12A2	ENST00000509205.5	c.*472C>T		3_prime_UTR_variant, NMD_transcript_variant	27/27	1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32264 AN: 151990 Hom.: 3581 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.228 AC: 57039 AN: 249672 Hom.: 6804 Cov.: 4 AF XY: 0.227 AC XY: 29124 AN XY: 128248

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.212 AC: 32292 AN: 152108 Hom.: 3590 Cov.: 32 AF XY: 0.216 AC XY: 16030 AN XY: 74362

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.208

Alfa AF: 0.210 Hom.: 7424

Bravo AF: 0.219

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs10089; hg19: chr5-127522543; COSMIC: COSV52478166; COSMIC: COSV52478166;