19-35249143-G-C

Position:

• chr19-35249143-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_205834.4(LSR):​c.109+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,524,882 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (10 hom.)
• Consequence: LSR NM_205834.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0930

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-35249143-G-C is Benign according to our data. Variant chr19-35249143-G-C is described in ClinVar as [Benign]. Clinvar id is 1988842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSR	NM_205834.4	c.109+12G>C		intron_variant		ENST00000605618.6	NP_991403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSR	ENST00000605618.6	c.109+12G>C		intron_variant		1	NM_205834.4	ENSP00000474797	A2

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 521 AN: 152224 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00412

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00388 AC: 455 AN: 117126 Hom.: 2 AF XY: 0.00366 AC XY: 235 AN XY: 64126

Gnomad AFR exome AF: 0.000669

Gnomad AMR exome AF: 0.000431

Gnomad ASJ exome AF: 0.00160

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000498

Gnomad FIN exome AF: 0.0165

Gnomad NFE exome AF: 0.00397

Gnomad OTH exome AF: 0.00345

GnomAD4 exome AF: 0.00410 AC: 5628 AN: 1372540 Hom.: 10 Cov.: 31 AF XY: 0.00397 AC XY: 2687 AN XY: 676924

Gnomad4 AFR exome AF: 0.000471

Gnomad4 AMR exome AF: 0.000486

Gnomad4 ASJ exome AF: 0.000919

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000613

Gnomad4 FIN exome AF: 0.0171

Gnomad4 NFE exome AF: 0.00425

Gnomad4 OTH exome AF: 0.00266

GnomAD4 genome AF: 0.00343 AC: 522 AN: 152342 Hom.: 2 Cov.: 33 AF XY: 0.00376 AC XY: 280 AN XY: 74492

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.00413

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00305 Hom.: 0

Bravo AF: 0.00211

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 14, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.1
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs200430113; hg19: chr19-35740046;