10-13645171-T-C

Variant names:

• chr10-13645171-T-C
• rs9473
• NM_018027.5:c.*1867A>G

Variant summary

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

The NM_018027.5(FRMD4A):​c.*1867A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,884 control chromosomes in the GnomAD database, including 26,939 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 0.59 (26936 hom., cov: 31)
  • Exomes 𝑓: 0.60 (3 hom.)
• Consequence: FRMD4A NM_018027.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.*1867A>G		3_prime_UTR_variant	Exon 25 of 25	ENST00000357447.7	NP_060497.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447	c.*1867A>G		3_prime_UTR_variant	Exon 25 of 25	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89971 AN: 151746 Hom.: 26911 Cov.: 31

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.600 AC: 12 AN: 20 Hom.: 3 Cov.: 0 AF XY: 0.643 AC XY: 9 AN XY: 14

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.593 AC: 90033 AN: 151864 Hom.: 26936 Cov.: 31 AF XY: 0.599 AC XY: 44468 AN XY: 74196

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.590

Alfa AF: 0.582 Hom.: 25449

Bravo AF: 0.592

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.82

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: rs9473; hg19: chr10-13687171;