Variant chr10-13693947-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_018027.5(FRMD4A):c.1068T>C(p.Gly356Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,596,308 control chromosomes in the GnomAD database, including 9,824 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 0.13 ( 1272 hom., cov: 30)

Exomes 𝑓: 0.11 ( 8552 hom. )

Consequence

FRMD4A
NM_018027.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.496

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:

FRMD4A (HGNC:):

FRMD4A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=-0.496 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5 linkuse as main transcript	c.1068T>C	p.Gly356Gly	synonymous_variant	15/25	ENST00000357447.7	NP_060497.3	Q9P2Q2
FRMD4A	NM_001318337.2 linkuse as main transcript	c.1167T>C	p.Gly389Gly	synonymous_variant	14/24		NP_001305266.1	Q9P2Q2
FRMD4A	NM_001318336.2 linkuse as main transcript	c.1116T>C	p.Gly372Gly	synonymous_variant	14/24		NP_001305265.1	Q9P2Q2Q9NW91
FRMD4A	NM_001318338.2 linkuse as main transcript	c.141T>C	p.Gly47Gly	synonymous_variant	4/14		NP_001305267.1	Q9P2Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7 linkuse as main transcript	c.1068T>C	p.Gly356Gly	synonymous_variant	15/25	1	NM_018027.5	ENSP00000350032.2		Q9P2Q2

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19132

AN:

150228

Hom.:

1262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0947

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.105

AC:

24842

AN:

236660

Hom.:

1419

AF XY:

0.105

AC XY:

13497

AN XY:

127964

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.0662

Gnomad ASJ exome

AF:

0.0850

Gnomad EAS exome

AF:

0.110

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.0881

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.0990

GnomAD4 exome

AF:

0.107

AC:

154823

AN:

1445960

Hom.:

8552

Cov.:

AF XY:

0.108

AC XY:

77578

AN XY:

718780

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.0696

Gnomad4 ASJ exome

AF:

0.0892

Gnomad4 EAS exome

AF:

0.0959

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.0896

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.128

AC:

19181

AN:

150348

Hom.:

1272

Cov.:

AF XY:

0.126

AC XY:

9222

AN XY:

73338

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0947

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.110

Hom.:

1535

Bravo

AF:

0.131

Asia WGS

AF:

0.120

AC:

419

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.2

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over