rs112086052

Variant names:

• chr19-17360628-G-A
• rs112086052
• NM_031310.3:c.1241-19C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-17360628-G-A
• chr19-17360628-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_031310.3(PLVAP):​c.1241-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,606,596 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.00072 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: PLVAP NM_031310.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.653
• Publications: 1 publications found

Genes affected

PLVAP (HGNC:13635): (plasmalemma vesicle associated protein) Predicted to enable identical protein binding activity. Involved in MAPK cascade; positive regulation of cellular extravasation; and tumor necrosis factor-mediated signaling pathway. Located in cell surface. Colocalizes with caveola. Implicated in congenital diarrhea. [provided by Alliance of Genome Resources, Apr 2022]

PLVAP Gene-Disease associations (from GenCC):

• diarrhea 10, protein-losing enteropathy type

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital diarrhea 7 with exudative enteropathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-17360628-G-A is Benign according to our data. Variant chr19-17360628-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1973330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000722 (110/152322) while in subpopulation AFR AF = 0.00236 (98/41568). AF 95% confidence interval is 0.00198. There are 1 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031310.3. 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
	PLVAP	NM_031310.3	MANE Select	c.1241-19C>T		intron	N/A	NP_112600.1	Q9BX97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLVAP	ENST00000252590.9	TSL:1 MANE Select	c.1241-19C>T		intron	N/A	ENSP00000252590.3	Q9BX97
	PLVAP	ENST00000962152.1		c.1241-19C>T		intron	N/A	ENSP00000632211.1
	PLVAP	ENST00000962153.1		c.1235-19C>T		intron	N/A	ENSP00000632212.1

Frequencies

GnomAD3 genomes AF: 0.000716 AC: 109 AN: 152204 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000163 AC: 40 AN: 245630 AF XY: 0.000121

Gnomad AFR exome AF: 0.00186

Gnomad AMR exome AF: 0.0000886

Gnomad ASJ exome AF: 0.000107

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.000109 AC: 158 AN: 1454274 Hom.: 0 Cov.: 31 AF XY: 0.0000967 AC XY: 70 AN XY: 723564

African (AFR) AF: 0.00309 AC: 103 AN: 33316

American (AMR) AF: 0.000226 AC: 10 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.000156 AC: 4 AN: 25606

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5664

European-Non Finnish (NFE) AF: 0.00000542 AC: 6 AN: 1106990

Other (OTH) AF: 0.000466 AC: 28 AN: 60048

GnomAD4 genome AF: 0.000722 AC: 110 AN: 152322 Hom.: 1 Cov.: 31 AF XY: 0.000806 AC XY: 60 AN XY: 74476

African (AFR) AF: 0.00236 AC: 98 AN: 41568

American (AMR) AF: 0.000588 AC: 9 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000855 Hom.: 0

Bravo AF: 0.000918

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Diarrhea 10, protein-losing enteropathy type (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.29
PhyloP100		-0.65
BranchPoint Hunter		3.0

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: rs112086052; hg19: chr19-17471437;