NM_000229.2:c.114C>G

Variant names:

• chr16-67943988-G-C
• NM_000229.2:c.114C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000229.2(LCAT):​c.114C>G​(p.Pro38Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LCAT NM_000229.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.923
• Publications: 0 publications found

Genes affected

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]

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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 16-67943988-G-C is Benign according to our data. Variant chr16-67943988-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1733526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.923 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000229.2. 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
	LCAT	NM_000229.2	MANE Select	c.114C>G	p.Pro38Pro	synonymous	Exon 1 of 6	NP_000220.1	P04180
	SLC12A4	NM_005072.5	MANE Select	c.*852C>G		3_prime_UTR	Exon 24 of 24	NP_005063.1	Q9UP95-1
	SLC12A4	NM_001145962.1		c.*852C>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
	LCAT	ENST00000264005.10	TSL:1 MANE Select	c.114C>G	p.Pro38Pro	synonymous	Exon 1 of 6	ENSP00000264005.5	P04180
	SLC12A4	ENST00000316341.8	TSL:1 MANE Select	c.*852C>G		3_prime_UTR	Exon 24 of 24	ENSP00000318557.3	Q9UP95-1
	LCAT	ENST00000575467.5	TSL:5	n.114C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000460653.1	I3L3R0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396414 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 688582

African (AFR) AF: 0.00 AC: 0 AN: 31552

American (AMR) AF: 0.00 AC: 0 AN: 35596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 35698

South Asian (SAS) AF: 0.00 AC: 0 AN: 79024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5048

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077846

Other (OTH) AF: 0.00 AC: 0 AN: 57804

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		0.92
PromoterAI		-0.031	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr16-67977891;