10-13986086-G-A

Position:

• chr10-13986086-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.46-127174C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,002 control chromosomes in the GnomAD database, including 23,407 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 0.52 (23407 hom., cov: 30)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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]

FRMD4A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.46-127174C>T		intron_variant		ENST00000357447.7	NP_060497.3
FRMD4A	NM_001318336.2	c.93+21974C>T		intron_variant			NP_001305265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.46-127174C>T		intron_variant		1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79334 AN: 151884 Hom.: 23369 Cov.: 30

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.523 AC: 79429 AN: 152002 Hom.: 23407 Cov.: 30 AF XY: 0.526 AC XY: 39078 AN XY: 74270

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.531

Alfa AF: 0.457 Hom.: 6232

Bravo AF: 0.554

Asia WGS AF: 0.771 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.87
DANN	Benign	0.32

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: rs2446585; hg19: chr10-14028086;