Genetic Variant LSR:p.Val25Phe (chr19-35249095-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_205834.4(LSR):c.73G>T(p.Val25Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,553,334 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

LSR
NM_205834.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0200

Variant links:

Genes affected

LSR (HGNC:29572): (lipolysis stimulated lipoprotein receptor) Predicted to be involved in several processes, including establishment of skin barrier; protein localization to tricellular tight junction; and tricellular tight junction assembly. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LSR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005397171).

BP6

Variant 19-35249095-G-T is Benign according to our data. Variant chr19-35249095-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2746821.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSR	NM_205834.4 link	c.73G>T	p.Val25Phe	missense_variant	Exon 1 of 10	ENST00000605618.6	NP_991403.2	Q86X29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSR	ENST00000605618.6 link	c.73G>T	p.Val25Phe	missense_variant	Exon 1 of 10	1	NM_205834.4	ENSP00000474797.2		S4R3V8

Frequencies

GnomAD3 genomes

AF:

0.000985

AC:

150

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

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:

0.00239

GnomAD3 exomes

AF:

0.000346

AC:

AN:

147342

Hom.:

AF XY:

0.000299

AC XY:

AN XY:

80330

show subpopulations

Gnomad AFR exome

AF:

0.00460

Gnomad AMR exome

AF:

0.000341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000148

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000128

AC:

179

AN:

1400990

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

692010

show subpopulations

Gnomad4 AFR exome

AF:

0.00350

Gnomad4 AMR exome

AF:

0.000344

Gnomad4 ASJ exome

AF:

0.0000796

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.0000305

Gnomad4 OTH exome

AF:

0.000328

GnomAD4 genome

AF:

0.000998

AC:

152

AN:

152344

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000195

Hom.:

Bravo

AF:

0.00124

ESP6500AA

AF:

0.00189

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000236

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

5.1

DANN

Benign

0.97

DEOGEN2

Benign

0.23

.;T;T;.;.;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.68

T;T;.;T;T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.0054

T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

L;L;L;L;L;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.1

.;.;N;N;N;N;.

REVEL

Benign

0.16

Sift

Benign

0.048

.;.;D;T;T;T;.

Sift4G

Benign

0.12

T;T;T;D;T;D;T

Polyphen

0.052

B;P;P;.;.;.;.

Vest4

0.19

MVP

0.44

MPC

0.26

ClinPred

0.0052

GERP RS

2.3

Varity_R

0.13

gMVP

0.38

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