rs898717

Variant names:

• chr10-14084114-T-C
• rs898717
• NM_018027.5:c.46-225202A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018027.5(FRMD4A):​c.46-225202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,036 control chromosomes in the GnomAD database, including 11,917 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 0.39 (11917 hom., cov: 32)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.22
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000235410 (HGNC:58386):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.46-225202A>G		intron_variant	Intron 2 of 24	ENST00000357447.7	NP_060497.3
FRMD4A-AS3	NR_120638.1	n.699+661T>C		intron_variant	Intron 2 of 2
FRMD4A	NR_134578.2	n.584-301A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.46-225202A>G		intron_variant	Intron 2 of 24	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59287 AN: 151918 Hom.: 11899 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.390 AC: 59349 AN: 152036 Hom.: 11917 Cov.: 32 AF XY: 0.392 AC XY: 29117 AN XY: 74324

African (AFR) AF: 0.426 AC: 17648 AN: 41450

American (AMR) AF: 0.438 AC: 6689 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1618 AN: 3468

East Asian (EAS) AF: 0.586 AC: 3021 AN: 5156

South Asian (SAS) AF: 0.393 AC: 1894 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3348 AN: 10574

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23785 AN: 67970

Other (OTH) AF: 0.395 AC: 836 AN: 2114

Alfa AF: 0.248 Hom.: 791

Bravo AF: 0.401

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0060
DANN	Benign	0.47
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs898717; hg19: chr10-14126113;