10-13876753-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018027.5(FRMD4A):c.46-17841A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,838 control chromosomes in the GnomAD database, including 7,056 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 0.29 (7056 hom., cov: 32)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.53

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4A	NM_018027.5	c.46-17841A>G		intron_variant		ENST00000357447.7
FRMD4A	NM_001318336.2	c.94-17841A>G		intron_variant
FRMD4A	NM_001318337.2	c.145-17841A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4A	ENST00000357447.7	c.46-17841A>G		intron_variant		1	NM_018027.5	P2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44221 AN: 151724 Hom.: 7058 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.291 AC: 44221 AN: 151838 Hom.: 7056 Cov.: 32 AF XY: 0.284 AC XY: 21068 AN XY: 74230

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.259

Alfa AF: 0.320 Hom.: 4310

Bravo AF: 0.289

Asia WGS AF: 0.269 AC: 937 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0040
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs10508468; hg19: chr10-13918753;