rs13005

Positions:

• chr10-13643766-G-A
• chr10-13643766-G-C
• chr10-13643766-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018027.5(FRMD4A):​c.*3272C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.56 in 152,516 control chromosomes in the GnomAD database, including 24,321 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 0.56 (24236 hom., cov: 33)
  • Exomes 𝑓: 0.64 (85 hom.)
• Consequence: FRMD4A NM_018027.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60

Genes affected

FRMD4A (HGNC:25491): (FERM domain containing 4A) This gene encodes a FERM domain-containing protein that regulates epithelial cell polarity. It connects ADP ribosylation factor 6 (ARF6) with the Par protein complex, which regulates the remodeling of adherens junctions and linear actin cable formation during epithelial cell polarization. Polymorphisms in this gene are associated with Alzheimer's disease, and also with nicotine dependence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

PRPF18 (HGNC:17351): (pre-mRNA processing factor 18) Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to the yeast splicing factor Prp18. [provided by RefSeq, Jul 2008]

PRPF18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.*3272C>T		3_prime_UTR_variant	25/25	ENST00000357447.7	NP_060497.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447	c.*3272C>T		3_prime_UTR_variant	25/25	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85110 AN: 151968 Hom.: 24214 Cov.: 33

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.637 AC: 274 AN: 430 Hom.: 85 Cov.: 0 AF XY: 0.658 AC XY: 171 AN XY: 260

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.560 AC: 85164 AN: 152086 Hom.: 24236 Cov.: 33 AF XY: 0.566 AC XY: 42099 AN XY: 74336

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.566

Alfa AF: 0.576 Hom.: 25252

Bravo AF: 0.557

Asia WGS AF: 0.583 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs13005; hg19: chr10-13685766;