NM_005072.5:c.1847+68T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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 = 0.379 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

African (AFR) AF: 0.404 AC: 13011 AN: 32204

American (AMR) AF: 0.0528 AC: 2358 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 1970 AN: 25744

East Asian (EAS) AF: 0.0116 AC: 458 AN: 39362

South Asian (SAS) AF: 0.0595 AC: 5057 AN: 85050

European-Finnish (FIN) AF: 0.0309 AC: 1612 AN: 52092

Middle Eastern (MID) AF: 0.148 AC: 833 AN: 5642

European-Non Finnish (NFE) AF: 0.0500 AC: 52806 AN: 1056998

Other (OTH) AF: 0.0775 AC: 4513 AN: 58262

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

African (AFR) AF: 0.384 AC: 15950 AN: 41516

American (AMR) AF: 0.0879 AC: 1345 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3470

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5170

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4822

European-Finnish (FIN) AF: 0.0268 AC: 285 AN: 10622

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.0495 AC: 3365 AN: 67970

Other (OTH) AF: 0.133 AC: 282 AN: 2114

Alfa AF: 0.0741 Hom.: 494

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
PhyloP100		-0.27
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: rs7200210; hg19: chr16-67981896;