19-35249088-C-T

Variant names:

• chr19-35249088-C-T
• rs765768043
• NM_205834.4:c.66C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_205834.4(LSR):​c.66C>T​(p.Asp22Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,404,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LSR NM_205834.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.837
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-35249088-C-T is Benign according to our data. Variant chr19-35249088-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2796679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.837 with no splicing effect.

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.66C>T	p.Asp22Asp	synonymous	Exon 1 of 10	NP_991403.2	S4R3V8
	LSR	NM_015925.7		c.66C>T	p.Asp22Asp	synonymous	Exon 1 of 9	NP_057009.4
	LSR	NM_001260489.2		c.66C>T	p.Asp22Asp	synonymous	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.66C>T	p.Asp22Asp	synonymous	Exon 1 of 10	ENSP00000474797.2	S4R3V8
	LSR	ENST00000621372.4	TSL:1	c.210C>T	p.Asp70Asp	synonymous	Exon 1 of 10	ENSP00000480821.1	Q86X29-1
	LSR	ENST00000361790.7	TSL:1	c.66C>T	p.Asp22Asp	synonymous	Exon 1 of 10	ENSP00000354575.3	S4R3V8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1404302 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 694032

African (AFR) AF: 0.00 AC: 0 AN: 31874

American (AMR) AF: 0.00 AC: 0 AN: 35238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 36590

South Asian (SAS) AF: 0.00 AC: 0 AN: 80562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4424

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1084106

Other (OTH) AF: 0.00 AC: 0 AN: 58052

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.6
DANN	Benign	0.86
PhyloP100		-0.84
PromoterAI		-0.22	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs765768043; hg19: chr19-35739991;