rs1181298236

Variant names:

• chr16-67943958-G-A
• rs1181298236
• NM_000229.2:c.144C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-67943958-G-A
• chr16-67943958-G-C
• chr16-67943958-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_000229.2(LCAT):​c.144C>T​(p.Pro48Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,546,898 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: LCAT NM_000229.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.636
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 16-67943958-G-A is Benign according to our data. Variant chr16-67943958-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3018303.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.636 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.144C>T	p.Pro48Pro	synonymous	Exon 1 of 6	NP_000220.1	P04180
	SLC12A4	NM_005072.5	MANE Select	c.*882C>T		3_prime_UTR	Exon 24 of 24	NP_005063.1	Q9UP95-1
	SLC12A4	NM_001145962.1		c.*882C>T		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.144C>T	p.Pro48Pro	synonymous	Exon 1 of 6	ENSP00000264005.5	P04180
	SLC12A4	ENST00000316341.8	TSL:1 MANE Select	c.*882C>T		3_prime_UTR	Exon 24 of 24	ENSP00000318557.3	Q9UP95-1
	LCAT	ENST00000575467.5	TSL:5	n.144C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000460653.1	I3L3R0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000651 AC: 1 AN: 153562 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000171

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000215 AC: 30 AN: 1394742 Hom.: 0 Cov.: 32 AF XY: 0.0000160 AC XY: 11 AN XY: 687604

African (AFR) AF: 0.00 AC: 0 AN: 31530

American (AMR) AF: 0.00 AC: 0 AN: 35500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25022

East Asian (EAS) AF: 0.000477 AC: 17 AN: 35666

South Asian (SAS) AF: 0.00 AC: 0 AN: 78864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4940

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1076698

Other (OTH) AF: 0.0000173 AC: 1 AN: 57762

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74328

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

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.1
DANN	Benign	0.90
PhyloP100		-0.64
PromoterAI		-0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1181298236; hg19: chr16-67977861;