10-13645171-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 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.*1867A>G		3_prime_UTR	Exon 25 of 25	NP_060497.3
	FRMD4A	NM_001318337.2		c.*1867A>G		3_prime_UTR	Exon 24 of 24	NP_001305266.1
	FRMD4A	NM_001318336.2		c.*1867A>G		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.*1867A>G		3_prime_UTR	Exon 25 of 25	ENSP00000350032.2	Q9P2Q2
	PRPF18	ENST00000601460.5	TSL:5	c.577-9182T>C		intron	N/A	ENSP00000473200.1	M0R3G1
	PRPF18	ENST00000440878.5	TSL:3	n.251+35T>C		intron	N/A

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

African (AFR) AF: 1.00 AC: 2 AN: 2

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: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AF: 0.333 AC: 2 AN: 6

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

African (AFR) AF: 0.561 AC: 23210 AN: 41374

American (AMR) AF: 0.620 AC: 9476 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1796 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4361 AN: 5150

South Asian (SAS) AF: 0.560 AC: 2684 AN: 4796

European-Finnish (FIN) AF: 0.666 AC: 7015 AN: 10530

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.581 AC: 39479 AN: 67950

Other (OTH) AF: 0.590 AC: 1246 AN: 2112

Alfa AF: 0.582 Hom.: 33218

Bravo AF: 0.592

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		-0.0090
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: rs9473; hg19: chr10-13687171;