rs2446581

chr10-13966445-G-A

Variant summary

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

The NM_018027.5(FRMD4A):c.46-107533C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,178 control chromosomes in the GnomAD database, including 9,041 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 0.27 (9041 hom., cov: 33)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4A	NM_018027.5	c.46-107533C>T		intron_variant		ENST00000357447.7
FRMD4A	NM_001318336.2	c.93+41615C>T		intron_variant
FRMD4A	NM_001318337.2	c.144+5211C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4A	ENST00000357447.7	c.46-107533C>T		intron_variant		1	NM_018027.5	P2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41639 AN: 152058 Hom.: 9027 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.274 AC: 41721 AN: 152178 Hom.: 9041 Cov.: 33 AF XY: 0.274 AC XY: 20405 AN XY: 74390

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.240

Alfa AF: 0.136 Hom.: 4033

Bravo AF: 0.298

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.60
Dann	Benign	0.86

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: rs2446581; hg19: chr10-14008445;