rs1109166

chr16-67943479-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005072.5(SLC12A4):c.*1361A>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 0.234 in 528,266 control chromosomes in the GnomAD database, including 20,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (11003 hom., cov: 33)
  • Exomes 𝑓: 0.20 (9262 hom.)
• Consequence: SLC12A4 NM_005072.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.132

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-67943479-T-C is Benign according to our data. Variant chr16-67943479-T-C is described in ClinVar as [Benign]. Clinvar id is 1221653.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-67943479-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A4	NM_005072.5	c.*1361A>G		3_prime_UTR_variant	24/24	ENST00000316341.8
LCAT	NM_000229.2	c.155-267A>G		intron_variant		ENST00000264005.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A4	ENST00000316341.8	c.*1361A>G		3_prime_UTR_variant	24/24	1	NM_005072.5	P1
LCAT	ENST00000264005.10	c.155-267A>G		intron_variant		1	NM_000229.2	P1
LCAT	ENST00000570980.1	c.-329A>G		5_prime_UTR_variant	1/5	2
LCAT	ENST00000575467.5	c.155-290A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47984 AN: 151972 Hom.: 10968 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.200 AC: 75377 AN: 376176 Hom.: 9262 Cov.: 0 AF XY: 0.201 AC XY: 39969 AN XY: 199076

Gnomad4 AFR exome AF: 0.645

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.316 AC: 48074 AN: 152090 Hom.: 11003 Cov.: 33 AF XY: 0.314 AC XY: 23334 AN XY: 74360

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.290

Alfa AF: 0.209 Hom.: 4065

Bravo AF: 0.329

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

This variant is associated with the following publications: (PMID: 31039173, 25814643) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.1
Dann	Benign	0.66

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: rs1109166; hg19: chr16-67977382;