rs11860115

Positions:

• chr16-67943793-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005072.5(SLC12A4):​c.*1047T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 697,360 control chromosomes in the GnomAD database, including 434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (308 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (126 hom.)
• Consequence: SLC12A4 NM_005072.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68

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]

LCAT (HGNC:6522): (lecithin-cholesterol acyltransferase) This gene encodes the extracellular cholesterol esterifying enzyme, lecithin-cholesterol acyltransferase. The esterification of cholesterol is required for cholesterol transport. Mutations in this gene have been found to cause fish-eye disease as well as LCAT deficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-67943793-A-C is Benign according to our data. Variant chr16-67943793-A-C is described in ClinVar as [Benign]. Clinvar id is 1282461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-67943793-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A4	NM_005072.5	c.*1047T>G		3_prime_UTR_variant	24/24	ENST00000316341.8	NP_005063.1
LCAT	NM_000229.2	c.154+155T>G		intron_variant		ENST00000264005.10	NP_000220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A4	ENST00000316341	c.*1047T>G		3_prime_UTR_variant	24/24	1	NM_005072.5	ENSP00000318557.3
LCAT	ENST00000264005.10	c.154+155T>G		intron_variant		1	NM_000229.2	ENSP00000264005.5
LCAT	ENST00000575467.5	n.154+155T>G		intron_variant		5		ENSP00000460653.1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5687 AN: 152092 Hom.: 306 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.0302

GnomAD4 exome AF: 0.00630 AC: 3436 AN: 545150 Hom.: 126 Cov.: 7 AF XY: 0.00572 AC XY: 1599 AN XY: 279580

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.0116

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000808

Gnomad4 FIN exome AF: 0.00269

Gnomad4 NFE exome AF: 0.00206

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0375 AC: 5701 AN: 152210 Hom.: 308 Cov.: 33 AF XY: 0.0361 AC XY: 2684 AN XY: 74406

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.00962 Hom.: 54

Bravo AF: 0.0420

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11860115; hg19: chr16-67977696;