10-14405340-T-C

Position:

• chr10-14405340-T-C

Variant summary

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

The ENST00000475141.2(FRMD4A):​c.-304-16437A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,100 control chromosomes in the GnomAD database, including 5,642 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 0.26 (5642 hom., cov: 32)
• Consequence: FRMD4A ENST00000475141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4A	ENST00000475141.2	c.-304-16437A>G		intron_variant		1
FRMD4A	ENST00000493380.5	c.-82+56728A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39112 AN: 151982 Hom.: 5629 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.257 AC: 39150 AN: 152100 Hom.: 5642 Cov.: 32 AF XY: 0.259 AC XY: 19244 AN XY: 74342

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.272

Alfa AF: 0.234 Hom.: 2037

Bravo AF: 0.265

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs649364; hg19: chr10-14447339;