16-67951803-C-T

Position:

• chr16-67951803-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000316341.8(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 ENST00000316341.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC12A4	NM_005072.5	c.1132+20G>A		intron_variant		ENST00000316341.8	NP_005063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A4	ENST00000316341.8	c.1132+20G>A		intron_variant		1	NM_005072.5	ENSP00000318557	P1

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

GnomAD3 exomes AF: 0.154 AC: 34535 AN: 224102 Hom.: 2797 AF XY: 0.152 AC XY: 18505 AN XY: 121476

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 SAS exome AF: 0.200

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

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.133

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

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.157

Alfa AF: 0.110 Hom.: 261

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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