16-67942417-A-T

Position:

chr16-67942417-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000229.2(LCAT):c.694T>A(p.Ser232Thr) variant causes a missense change. The variant allele was found at a frequency of 0.026 in 1,613,908 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 31 hom., cov: 32)

Exomes 𝑓: 0.027 ( 619 hom. )

Consequence

LCAT
NM_000229.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.82

Variant links:

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]

LCAT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011052489).

BP6

Variant 16-67942417-A-T is Benign according to our data. Variant chr16-67942417-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 884653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-67942417-A-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0173 (2627/152236) while in subpopulation NFE AF= 0.0287 (1952/67990). AF 95% confidence interval is 0.0276. There are 31 homozygotes in gnomad4. There are 1221 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCAT	NM_000229.2 linkuse as main transcript	c.694T>A	p.Ser232Thr	missense_variant	5/6	ENST00000264005.10	NP_000220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCAT	ENST00000264005.10 linkuse as main transcript	c.694T>A	p.Ser232Thr	missense_variant	5/6	1	NM_000229.2	ENSP00000264005	P1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2628

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00493

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.0175

AC:

4389

AN:

251330

Hom.:

AF XY:

0.0175

AC XY:

2381

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00486

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00562

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0289

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.0269

AC:

39307

AN:

1461672

Hom.:

619

Cov.:

AF XY:

0.0261

AC XY:

18971

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00406

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00645

Gnomad4 FIN exome

AF:

0.0270

Gnomad4 NFE exome

AF:

0.0321

Gnomad4 OTH exome

AF:

0.0199

GnomAD4 genome

AF:

0.0173

AC:

2627

AN:

152236

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1221

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00491

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.0271

Gnomad4 NFE

AF:

0.0287

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0155

TwinsUK

AF:

0.0291

AC:

108

ALSPAC

AF:

0.0283

AC:

109

ESP6500AA

AF:

0.00660

AC:

ESP6500EA

AF:

0.0306

AC:

263

ExAC

AF:

0.0180

AC:

2188

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0235

EpiControl

AF:

0.0228

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 23, 2020	This variant is associated with the following publications: (PMID: 22090275, 24503134) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

LCAT deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

LCAT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Norum disease;C0342895:Fish-eye disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 06, 2022

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2019

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Uncertain

0.53

D;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.6

N;.

REVEL

Uncertain

0.57

Sift

Benign

0.19

T;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.98

D;.

Vest4

0.23

MPC

0.53

ClinPred

0.031

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over