16-67951803-C-T

Variant names:

• chr16-67951803-C-T
• rs2292318
• NM_005072.5:c.1132+20G>A

Variant summary

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

The NM_005072.5(SLC12A4):​c.1132+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,592,484 control chromosomes in the GnomAD database, including 15,649 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 0.16 (2114 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13535 hom.)
• Consequence: SLC12A4 NM_005072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 34 publications found

Genes affected

SLC12A4 (HGNC:10913): (solute carrier family 12 member 4) This gene encodes a member of the SLC12A transporter family. The encoded protein mediates the coupled movement of potassium and chloride ions across the plasma membrane. This gene is expressed ubiquitously. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A4	NM_005072.5	c.1132+20G>A		intron_variant	Intron 8 of 23	ENST00000316341.8	NP_005063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A4	ENST00000316341.8	c.1132+20G>A		intron_variant	Intron 8 of 23	1	NM_005072.5	ENSP00000318557.3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24400 AN: 152042 Hom.: 2115 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.154 AC: 34535 AN: 224102 AF XY: 0.152

Gnomad AFR exome AF: 0.228

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.133 AC: 191822 AN: 1440324 Hom.: 13535 Cov.: 30 AF XY: 0.135 AC XY: 96515 AN XY: 715648

African (AFR) AF: 0.211 AC: 6997 AN: 33188

American (AMR) AF: 0.164 AC: 6833 AN: 41580

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4149 AN: 25662

East Asian (EAS) AF: 0.125 AC: 4870 AN: 39042

South Asian (SAS) AF: 0.192 AC: 16171 AN: 84374

European-Finnish (FIN) AF: 0.163 AC: 8462 AN: 51818

Middle Eastern (MID) AF: 0.120 AC: 609 AN: 5072

European-Non Finnish (NFE) AF: 0.123 AC: 135834 AN: 1100032

Other (OTH) AF: 0.133 AC: 7897 AN: 59556

GnomAD4 genome AF: 0.160 AC: 24410 AN: 152160 Hom.: 2114 Cov.: 32 AF XY: 0.163 AC XY: 12143 AN XY: 74386

African (AFR) AF: 0.218 AC: 9057 AN: 41488

American (AMR) AF: 0.152 AC: 2327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3468

East Asian (EAS) AF: 0.103 AC: 534 AN: 5186

South Asian (SAS) AF: 0.188 AC: 908 AN: 4822

European-Finnish (FIN) AF: 0.171 AC: 1810 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8642 AN: 67998

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.143 Hom.: 563

Bravo AF: 0.161

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.70
PhyloP100		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2292318; hg19: chr16-67985706; COSMIC: COSV57928666; COSMIC: COSV57928666;