16-67947993-A-G

Variant names:

• chr16-67947993-A-G
• rs7200210
• NM_005072.5:c.1847+68T>C

Variant summary

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

The NM_005072.5(SLC12A4):​c.1847+68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,552,186 control chromosomes in the GnomAD database, including 8,050 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 0.14 (3246 hom., cov: 33)
  • Exomes 𝑓: 0.059 (4804 hom.)
• Consequence: SLC12A4 NM_005072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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 = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A4	NM_005072.5	c.1847+68T>C		intron_variant	Intron 14 of 23	ENST00000316341.8	NP_005063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A4	ENST00000316341.8	c.1847+68T>C		intron_variant	Intron 14 of 23	1	NM_005072.5	ENSP00000318557.3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21858 AN: 152078 Hom.: 3232 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0881

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.0590 AC: 82618 AN: 1399990 Hom.: 4804 Cov.: 24 AF XY: 0.0582 AC XY: 40772 AN XY: 700008

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.0528

Gnomad4 ASJ exome AF: 0.0765

Gnomad4 EAS exome AF: 0.0116

Gnomad4 SAS exome AF: 0.0595

Gnomad4 FIN exome AF: 0.0309

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.0775

GnomAD4 genome AF: 0.144 AC: 21915 AN: 152196 Hom.: 3246 Cov.: 33 AF XY: 0.140 AC XY: 10397 AN XY: 74424

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0566

Gnomad4 FIN AF: 0.0268

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0715 Hom.: 406

Bravo AF: 0.155

Asia WGS AF: 0.0610 AC: 211 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	1.4
DANN	Benign	0.54

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: rs7200210; hg19: chr16-67981896;