dbSNP rs13005: FRMD4A:c.*3272C>T (chr10-13643766-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_018027.5(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
NM_018027.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.60

Publications

9 publications found

Variant links:

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]

FRMD4A links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5 link	c.*3272C>T		3_prime_UTR_variant	Exon 25 of 25	ENST00000357447.7	NP_060497.3	Q9P2Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7 link	c.*3272C>T		3_prime_UTR_variant	Exon 25 of 25	1	NM_018027.5	ENSP00000350032.2		Q9P2Q2

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85110

AN:

151968

Hom.:

24214

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.658

AC XY:

171

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.637

AC:

270

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.560

AC:

85164

AN:

152086

Hom.:

24236

Cov.:

AF XY:

0.566

AC XY:

42099

AN XY:

74336

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1966

3931

5897

7862

9828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

5.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs13005

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over