rs1109166

Variant names:

• chr16-67943479-T-A
• rs1109166
• NM_005072.5:c.*1361A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-67943479-T-A
• chr16-67943479-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005072.5(SLC12A4):​c.*1361A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000266 in 376,560 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC12A4 NM_005072.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• LCAT deficiency

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A4	NM_005072.5	c.*1361A>T		3_prime_UTR_variant	Exon 24 of 24	ENST00000316341.8	NP_005063.1
LCAT	NM_000229.2	c.155-267A>T		intron_variant	Intron 1 of 5	ENST00000264005.10	NP_000220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A4	ENST00000316341.8	c.*1361A>T		3_prime_UTR_variant	Exon 24 of 24	1	NM_005072.5	ENSP00000318557.3
LCAT	ENST00000264005.10	c.155-267A>T		intron_variant	Intron 1 of 5	1	NM_000229.2	ENSP00000264005.5
LCAT	ENST00000570980.1	c.-329A>T		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000464651.1
LCAT	ENST00000575467.5	n.155-290A>T		intron_variant	Intron 1 of 5	5		ENSP00000460653.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000266 AC: 1 AN: 376560 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 199274

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10978

American (AMR) AF: 0.00 AC: 0 AN: 16684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11668

East Asian (EAS) AF: 0.00 AC: 0 AN: 23538

South Asian (SAS) AF: 0.00 AC: 0 AN: 45332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1626

European-Non Finnish (NFE) AF: 0.00000448 AC: 1 AN: 222996

Other (OTH) AF: 0.00 AC: 0 AN: 21790

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.72
PhyloP100		0.13
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs1109166; hg19: chr16-67977382;