19-35248900-G-A

Variant names:

• chr19-35248900-G-A
• ENST00000621372.4:c.22G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000621372.4(LSR):​c.22G>A​(p.Val8Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LSR ENST00000621372.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.583

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02663228).
• BP6: Variant 19-35248900-G-A is Benign according to our data. Variant chr19-35248900-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3868890.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	c.-123G>A		upstream_gene_variant		ENST00000605618.6	NP_991403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSR	ENST00000605618.6	c.-123G>A		upstream_gene_variant		1	NM_205834.4	ENSP00000474797.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 20, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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	0.076
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.82
DANN	Benign	0.87
DEOGEN2	Benign	0.079	.;T;T;.;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.64	T;T;.;T;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.027	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;N;N;.;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.050	.;.;N;.;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.99	.;.;T;.;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		0.0	B;B;B;.;.;.;B
Vest4		0.069
MutPred		0.27		Loss of MoRF binding (P = 0.1025);Loss of MoRF binding (P = 0.1025);Loss of MoRF binding (P = 0.1025);Loss of MoRF binding (P = 0.1025);Loss of MoRF binding (P = 0.1025);Loss of MoRF binding (P = 0.1025);Loss of MoRF binding (P = 0.1025);
MVP		0.081
MPC		0.15
ClinPred		0.057	T
GERP RS		-1.9
Varity_R		0.026
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35739803;