rs7082219

Positions:

• chr10-14333260-G-T

Variant summary

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

The ENST00000475141.2(FRMD4A):​c.-81-3077C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,770 control chromosomes in the GnomAD database, including 5,501 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 (5501 hom., cov: 30)
• Consequence: FRMD4A ENST00000475141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000475141.2	c.-81-3077C>A		intron_variant		1		ENSP00000473870
FRMD4A	ENST00000493380.5	c.-81-3077C>A		intron_variant		1		ENSP00000474863

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38889 AN: 151652 Hom.: 5506 Cov.: 30

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.256 AC: 38897 AN: 151770 Hom.: 5501 Cov.: 30 AF XY: 0.261 AC XY: 19327 AN XY: 74132

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.301

Alfa AF: 0.290 Hom.: 11018

Bravo AF: 0.249

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.25
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7082219; hg19: chr10-14375259;