rs56161216

Variant names:

• chr10-13646798-A-G
• rs56161216
• NM_018027.5:c.*240T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018027.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	NM_018027.5	MANE Select	c.*240T>C		3_prime_UTR	Exon 25 of 25	NP_060497.3
	FRMD4A	NM_001318337.2		c.*240T>C		3_prime_UTR	Exon 24 of 24	NP_001305266.1
	FRMD4A	NM_001318336.2		c.*240T>C		3_prime_UTR	Exon 24 of 24	NP_001305265.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	ENST00000357447.7	TSL:1 MANE Select	c.*240T>C		3_prime_UTR	Exon 25 of 25	ENSP00000350032.2	Q9P2Q2
	FRMD4A	ENST00000495956.3	TSL:2	c.*135T>C		3_prime_UTR	Exon 24 of 24	ENSP00000488764.2	A0A0J9YYA7
	PRPF18	ENST00000601460.5	TSL:5	c.577-7555A>G		intron	N/A	ENSP00000473200.1	M0R3G1

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

African (AFR) AF: 0.00 AC: 0 AN: 12

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.0588 AC: 2 AN: 34

European-Finnish (FIN) AF: 0.0479 AC: 21 AN: 438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1188

Other (OTH) AF: 0.0192 AC: 1 AN: 52

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

African (AFR) AF: 0.145 AC: 6027 AN: 41486

American (AMR) AF: 0.0173 AC: 264 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.0591 AC: 306 AN: 5176

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4824

European-Finnish (FIN) AF: 0.0308 AC: 327 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 68016

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0330 Hom.: 56

Bravo AF: 0.0509

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.52
PhyloP100		0.23
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: rs56161216; hg19: chr10-13688798;