rs11628713

Variant names:

• chr14-73255067-C-T
• rs11628713
• NM_001365906.3:c.1627+49C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365906.3(PAPLN):​c.1627+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,571,484 control chromosomes in the GnomAD database, including 23,507 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2083 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21424 hom.)
• Consequence: PAPLN NM_001365906.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 18 publications found

Genes affected

PAPLN (HGNC:19262): (papilin, proteoglycan like sulfated glycoprotein) Predicted to enable metalloendopeptidase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in basement membrane. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.1627+49C>T		intron_variant	Intron 14 of 26	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.1627+49C>T		intron_variant	Intron 14 of 26		NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24476 AN: 152050 Hom.: 2083 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.163 AC: 30483 AN: 186612 AF XY: 0.170

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.0909

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.171 AC: 242920 AN: 1419314 Hom.: 21424 Cov.: 33 AF XY: 0.173 AC XY: 121625 AN XY: 702308

African (AFR) AF: 0.143 AC: 4628 AN: 32334

American (AMR) AF: 0.0946 AC: 3661 AN: 38698

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4253 AN: 25226

East Asian (EAS) AF: 0.0876 AC: 3252 AN: 37138

South Asian (SAS) AF: 0.199 AC: 16264 AN: 81900

European-Finnish (FIN) AF: 0.162 AC: 8045 AN: 49690

Middle Eastern (MID) AF: 0.229 AC: 1302 AN: 5680

European-Non Finnish (NFE) AF: 0.176 AC: 191329 AN: 1089882

Other (OTH) AF: 0.173 AC: 10186 AN: 58766

GnomAD4 genome AF: 0.161 AC: 24502 AN: 152170 Hom.: 2083 Cov.: 32 AF XY: 0.161 AC XY: 11956 AN XY: 74390

African (AFR) AF: 0.147 AC: 6094 AN: 41512

American (AMR) AF: 0.118 AC: 1803 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3472

East Asian (EAS) AF: 0.0924 AC: 478 AN: 5174

South Asian (SAS) AF: 0.193 AC: 934 AN: 4828

European-Finnish (FIN) AF: 0.161 AC: 1711 AN: 10598

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12357 AN: 67970

Other (OTH) AF: 0.163 AC: 345 AN: 2114

Alfa AF: 0.173 Hom.: 7409

Bravo AF: 0.155

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.45
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs11628713; hg19: chr14-73721775; COSMIC: COSV53723544; COSMIC: COSV53723544;