chr10-13643766-G-A

Variant names:

• chr10-13643766-G-A
• rs13005
• NM_018027.5:c.*3272C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000357447.7(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 ENST00000357447.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60
• Publications: 9 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357447.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	NM_018027.5	MANE Select	c.*3272C>T		3_prime_UTR	Exon 25 of 25	NP_060497.3
	FRMD4A	NM_001318337.2		c.*3272C>T		3_prime_UTR	Exon 24 of 24	NP_001305266.1
	FRMD4A	NM_001318336.2		c.*3272C>T		3_prime_UTR	Exon 24 of 24	NP_001305265.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	ENST00000357447.7	TSL:1 MANE Select	c.*3272C>T		3_prime_UTR	Exon 25 of 25	ENSP00000350032.2
	PRPF18	ENST00000601460.5	TSL:5	c.577-10587G>A		intron	N/A	ENSP00000473200.1
	PRPF18	ENST00000440878.5	TSL:3	n.32-1151G>A		intron	N/A

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

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) AF: 0.637 AC: 270 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.471 AC: 19545 AN: 41480

American (AMR) AF: 0.606 AC: 9253 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1734 AN: 3466

East Asian (EAS) AF: 0.788 AC: 4080 AN: 5180

South Asian (SAS) AF: 0.540 AC: 2606 AN: 4830

European-Finnish (FIN) AF: 0.636 AC: 6717 AN: 10568

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39314 AN: 67972

Other (OTH) AF: 0.566 AC: 1196 AN: 2112

Alfa AF: 0.574 Hom.: 29879

Bravo AF: 0.557

Asia WGS AF: 0.583 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		5.6
Mutation Taster		=99/1	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: rs13005; hg19: chr10-13685766;