rs200943005

Variant names:

• chr19-35249095-G-A
• rs200943005
• NM_205834.4:c.73G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35249095-G-A
• chr19-35249095-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_205834.4(LSR):​c.73G>A​(p.Val25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,400,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V25F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LSR NM_205834.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0200
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052263826).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205834.4. 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
	LSR	NM_205834.4	MANE Select	c.73G>A	p.Val25Ile	missense	Exon 1 of 10	NP_991403.2	S4R3V8
	LSR	NM_015925.7		c.73G>A	p.Val25Ile	missense	Exon 1 of 9	NP_057009.4
	LSR	NM_001260489.2		c.73G>A	p.Val25Ile	missense	Exon 1 of 9	NP_001247418.2	A0A8Z5DL71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSR	ENST00000605618.6	TSL:1 MANE Select	c.73G>A	p.Val25Ile	missense	Exon 1 of 10	ENSP00000474797.2	S4R3V8
	LSR	ENST00000621372.4	TSL:1	c.217G>A	p.Val73Ile	missense	Exon 1 of 10	ENSP00000480821.1	Q86X29-1
	LSR	ENST00000361790.7	TSL:1	c.73G>A	p.Val25Ile	missense	Exon 1 of 10	ENSP00000354575.3	S4R3V8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1400988 Hom.: 0 Cov.: 31 AF XY: 0.00000434 AC XY: 3 AN XY: 692008

African (AFR) AF: 0.00 AC: 0 AN: 31736

American (AMR) AF: 0.00 AC: 0 AN: 34864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25122

East Asian (EAS) AF: 0.00 AC: 0 AN: 36366

South Asian (SAS) AF: 0.00 AC: 0 AN: 80102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4332

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1082416

Other (OTH) AF: 0.00 AC: 0 AN: 57908

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.5
DANN	Benign	0.96
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.020
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.028
Sift	Benign	0.65	T
Sift4G	Benign	0.85	T
Polyphen		0.0040	B
Vest4		0.073
MutPred		0.21		Gain of catalytic residue at L78 (P = 0.0651)
MVP		0.17
MPC		0.15
ClinPred		0.035	T
GERP RS		2.3
PromoterAI		-0.0061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.035
gMVP		0.18
Mutation Taster		=99/1	polymorphism

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: rs200943005; hg19: chr19-35739998;