rs922239

Positions:

• chr10-14083636-A-T

Variant summary

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

The ENST00000493380.5(FRMD4A):​c.*190T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,156 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4173 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: FRMD4A ENST00000493380.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.46-224724T>A		intron_variant		ENST00000357447.7	NP_060497.3
LOC101928453	NR_120638.1	n.699+183A>T		intron_variant, non_coding_transcript_variant
FRMD4A	NR_134578.2	n.761T>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.46-224724T>A		intron_variant		1	NM_018027.5	ENSP00000350032	P2
	ENST00000451617.1	n.699+183A>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34479 AN: 152010 Hom.: 4171 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.179 AC: 5 AN: 28 Hom.: 1 Cov.: 0 AF XY: 0.182 AC XY: 4 AN XY: 22

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.208

GnomAD4 genome AF: 0.227 AC: 34499 AN: 152128 Hom.: 4173 Cov.: 33 AF XY: 0.231 AC XY: 17180 AN XY: 74366

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.230

Alfa AF: 0.222 Hom.: 461

Bravo AF: 0.227

Asia WGS AF: 0.289 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.59

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: rs922239; hg19: chr10-14125635;