rs1047849

Variant names:

• chr14-73274478-T-C
• rs1047849
• ENST00000555700.1:n.4523T>C

Variant summary

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

The ENST00000555700.1(PAPLN):​n.4523T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,208 control chromosomes in the GnomAD database, including 2,738 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 (2738 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PAPLN ENST00000555700.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.*1814T>C		3_prime_UTR_variant	Exon 27 of 27	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.*1814T>C		3_prime_UTR_variant	Exon 27 of 27		NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23995 AN: 152088 Hom.: 2738 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.158 AC: 23991 AN: 152206 Hom.: 2738 Cov.: 32 AF XY: 0.156 AC XY: 11639 AN XY: 74408

African (AFR) AF: 0.0404 AC: 1677 AN: 41552

American (AMR) AF: 0.119 AC: 1818 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3464

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5192

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4828

European-Finnish (FIN) AF: 0.329 AC: 3472 AN: 10556

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15833 AN: 68000

Other (OTH) AF: 0.144 AC: 303 AN: 2110

Alfa AF: 0.199 Hom.: 5522

Bravo AF: 0.142

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.77
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1047849; hg19: chr14-73741186;