Genetic Variant LSR:p.His15Asp (chr19-35249065-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_205834.4(LSR):c.43C>G(p.His15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,417,066 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H15Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LSR
NM_205834.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08132258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSR	NM_205834.4 link	c.43C>G	p.His15Asp	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.43C>G	p.His15Asp	missense_variant	Exon 1 of 10	1	NM_205834.4	ENSP00000474797.2		S4R3V8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000605

AC:

AN:

165344

AF XY:

0.0000110

show subpopulations

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:

0.0000154

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.06e-7

AC:

AN:

1417066

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32336

American (AMR)

AF:

0.00

AC:

AN:

36872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25364

East Asian (EAS)

AF:

0.00

AC:

AN:

37380

South Asian (SAS)

AF:

0.00

AC:

AN:

82248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4650

European-Non Finnish (NFE)

AF:

9.17e-7

AC:

AN:

1090802

Other (OTH)

AF:

0.00

AC:

AN:

58526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.1

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.15

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.47

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

M_CAP

Benign

0.034

MetaRNN

Benign

0.081

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

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

PhyloP100

-2.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

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

REVEL

Benign

0.077

Sift

Uncertain

0.015

.;.;D;D;D;D;.

Sift4G

Benign

0.17

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

Polyphen

0.0

B;B;B;.;.;.;.

Vest4

0.19

MutPred

0.22

Loss of methylation at R58 (P = 0.0722);Loss of methylation at R58 (P = 0.0722);Loss of methylation at R58 (P = 0.0722);Loss of methylation at R58 (P = 0.0722);Loss of methylation at R58 (P = 0.0722);.;.;

MVP

0.31

MPC

0.27

ClinPred

0.041

GERP RS

-2.1

PromoterAI

0.18

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.34

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over