rs942943

Positions:

• chr10-14422368-C-T

Variant summary

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

The ENST00000475141.2(FRMD4A):​c.-304-33465G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 152,190 control chromosomes in the GnomAD database, including 311 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 0.041 (311 hom., cov: 31)
• Consequence: FRMD4A ENST00000475141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 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.-304-33465G>A		intron_variant		1
FRMD4A	ENST00000493380.5	c.-82+39700G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6246 AN: 152072 Hom.: 310 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00620

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0411 AC: 6259 AN: 152190 Hom.: 311 Cov.: 31 AF XY: 0.0412 AC XY: 3063 AN XY: 74392

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.0926

Gnomad4 SAS AF: 0.0237

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.00619

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0251 Hom.: 18

Bravo AF: 0.0474

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs942943; hg19: chr10-14464367;