rs990170742

Variant names:

• chr11-1890570-A-G
• rs990170742
• NM_001395380.1:c.15T>C

Variant summary

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

The NM_001395380.1(PRR33):​c.15T>C​(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 708,914 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: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: PRR33 NM_001395380.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25
• Publications: 0 publications found

Genes affected

PRR33 (HGNC:35118): (proline rich 33) Predicted to act upstream of or within response to wounding. [provided by Alliance of Genome Resources, Apr 2022]

LSP1 (HGNC:6707): (lymphocyte specific protein 1) This gene encodes an intracellular F-actin binding protein. The protein is expressed in lymphocytes, neutrophils, macrophages, and endothelium and may regulate neutrophil motility, adhesion to fibrinogen matrix proteins, and transendothelial migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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=-0.94).
• BP6: Variant 11-1890570-A-G is Benign according to our data. Variant chr11-1890570-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2641352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.25 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395380.1. 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
	PRR33	NM_001395380.1	MANE Select	c.15T>C	p.Ala5Ala	synonymous	Exon 1 of 1	NP_001382309.1	A0A1W2PPC1
	LSP1	NM_002339.3	MANE Select	c.*14-1203A>G		intron	N/A	NP_002330.1	P33241-1
	LSP1	NM_001242932.2		c.*14-1203A>G		intron	N/A	NP_001229861.1	P33241-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR33	ENST00000640310.2	TSL:6 MANE Select	c.15T>C	p.Ala5Ala	synonymous	Exon 1 of 1	ENSP00000491327.1	A0A1W2PPC1
	LSP1	ENST00000311604.8	TSL:1 MANE Select	c.*14-1203A>G		intron	N/A	ENSP00000308383.4	P33241-1
	LSP1	ENST00000381775.5	TSL:2	c.*14-1203A>G		intron	N/A	ENSP00000371194.1	P33241-3

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152052 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000105 AC: 15 AN: 142324 AF XY: 0.0000907

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000862 AC: 48 AN: 556862 Hom.: 0 Cov.: 0 AF XY: 0.0000764 AC XY: 23 AN XY: 301176

African (AFR) AF: 0.00 AC: 0 AN: 15796

American (AMR) AF: 0.000115 AC: 4 AN: 34706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20006

East Asian (EAS) AF: 0.00 AC: 0 AN: 32102

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 62744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3702

European-Non Finnish (NFE) AF: 0.000129 AC: 41 AN: 316936

Other (OTH) AF: 0.0000654 AC: 2 AN: 30602

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152052 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74266

African (AFR) AF: 0.0000483 AC: 2 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67954

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000797 Hom.: 0

Bravo AF: 0.0000831

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	-0.94
CADD	Benign	0.67
DANN	Benign	0.22
PhyloP100		-2.3

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: rs990170742; hg19: chr11-1911800;