chr16-67943793-A-C

Variant names:

• chr16-67943793-A-C
• rs11860115
• NM_005072.5:c.*1047T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

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]

LCAT Gene-Disease associations (from GenCC):

• fish eye disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• LCAT deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• Norum disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1282461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005072.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A4	NM_005072.5	MANE Select	c.*1047T>G		3_prime_UTR	Exon 24 of 24	NP_005063.1	Q9UP95-1
	LCAT	NM_000229.2	MANE Select	c.154+155T>G		intron	N/A	NP_000220.1	P04180
	SLC12A4	NM_001145962.1		c.*1047T>G		3_prime_UTR	Exon 23 of 23	NP_001139434.1	Q9UP95-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A4	ENST00000316341.8	TSL:1 MANE Select	c.*1047T>G		3_prime_UTR	Exon 24 of 24	ENSP00000318557.3	Q9UP95-1
	LCAT	ENST00000264005.10	TSL:1 MANE Select	c.154+155T>G		intron	N/A	ENSP00000264005.5	P04180
	LCAT	ENST00000575467.5	TSL:5	n.154+155T>G		intron	N/A	ENSP00000460653.1	I3L3R0

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

African (AFR) AF: 0.128 AC: 1804 AN: 14102

American (AMR) AF: 0.0116 AC: 206 AN: 17788

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 167 AN: 13998

East Asian (EAS) AF: 0.00 AC: 0 AN: 30798

South Asian (SAS) AF: 0.000808 AC: 35 AN: 43310

European-Finnish (FIN) AF: 0.00269 AC: 105 AN: 39086

Middle Eastern (MID) AF: 0.0182 AC: 38 AN: 2088

European-Non Finnish (NFE) AF: 0.00206 AC: 731 AN: 355284

Other (OTH) AF: 0.0122 AC: 350 AN: 28696

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

African (AFR) AF: 0.125 AC: 5175 AN: 41500

American (AMR) AF: 0.0165 AC: 252 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00206 AC: 140 AN: 68008

Other (OTH) AF: 0.0294 AC: 62 AN: 2110

Alfa AF: 0.0147 Hom.: 120

Bravo AF: 0.0420

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-1.7
PromoterAI		0.00010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11860115; hg19: chr16-67977696;