10-13724692-G-A

Variant names:

• chr10-13724692-G-A
• rs2015015
• NM_018027.5:c.759+13152C>T

Variant summary

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

The NM_018027.5(FRMD4A):​c.759+13152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,098 control chromosomes in the GnomAD database, including 9,801 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 0.36 (9801 hom., cov: 32)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 5 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

ENSG00000225112 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.759+13152C>T		intron_variant	Intron 12 of 24	ENST00000357447.7	NP_060497.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.759+13152C>T		intron_variant	Intron 12 of 24	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54243 AN: 151980 Hom.: 9794 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.357 AC: 54287 AN: 152098 Hom.: 9801 Cov.: 32 AF XY: 0.364 AC XY: 27069 AN XY: 74334

African (AFR) AF: 0.351 AC: 14548 AN: 41502

American (AMR) AF: 0.402 AC: 6147 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3464

East Asian (EAS) AF: 0.433 AC: 2240 AN: 5172

South Asian (SAS) AF: 0.418 AC: 2015 AN: 4816

European-Finnish (FIN) AF: 0.398 AC: 4204 AN: 10566

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22871 AN: 67976

Other (OTH) AF: 0.366 AC: 773 AN: 2114

Alfa AF: 0.348 Hom.: 16180

Bravo AF: 0.361

Asia WGS AF: 0.389 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.34
PhyloP100		1.0
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: rs2015015; hg19: chr10-13766692;