rs56161216

Positions:

• chr10-13646798-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018027.5(FRMD4A):​c.*240T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 153,940 control chromosomes in the GnomAD database, including 500 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 0.048 (499 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1 hom.)
• Consequence: FRMD4A NM_018027.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.*240T>C		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.*240T>C		3_prime_UTR_variant	25/25	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.0481 AC: 7311 AN: 152070 Hom.: 497 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0137 AC: 24 AN: 1752 Hom.: 1 Cov.: 0 AF XY: 0.00967 AC XY: 10 AN XY: 1034

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0588

Gnomad4 FIN exome AF: 0.0479

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0482 AC: 7329 AN: 152188 Hom.: 499 Cov.: 32 AF XY: 0.0478 AC XY: 3555 AN XY: 74408

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0283 Hom.: 44

Bravo AF: 0.0509

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.52

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: rs56161216; hg19: chr10-13688798;