rs1541010

Variant names:

• chr10-13713544-C-T
• rs1541010
• NM_018027.5:c.760-6431G>A

Variant summary

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

The NM_018027.5(FRMD4A):​c.760-6431G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,674 control chromosomes in the GnomAD database, including 6,047 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 0.28 (6047 hom., cov: 30)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 13 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.760-6431G>A		intron_variant	Intron 12 of 24	ENST00000357447.7	NP_060497.3
FRMD4A	NM_001318337.2	c.859-6431G>A		intron_variant	Intron 11 of 23		NP_001305266.1
FRMD4A	NM_001318336.2	c.808-6431G>A		intron_variant	Intron 11 of 23		NP_001305265.1
LOC105376426	XR_001747371.2	n.260+1530C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.760-6431G>A		intron_variant	Intron 12 of 24	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42170 AN: 151556 Hom.: 6041 Cov.: 30

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.278 AC: 42199 AN: 151674 Hom.: 6047 Cov.: 30 AF XY: 0.277 AC XY: 20540 AN XY: 74090

African (AFR) AF: 0.319 AC: 13199 AN: 41322

American (AMR) AF: 0.213 AC: 3236 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3464

East Asian (EAS) AF: 0.153 AC: 793 AN: 5172

South Asian (SAS) AF: 0.186 AC: 895 AN: 4818

European-Finnish (FIN) AF: 0.346 AC: 3623 AN: 10466

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18866 AN: 67950

Other (OTH) AF: 0.258 AC: 542 AN: 2102

Alfa AF: 0.272 Hom.: 12646

Bravo AF: 0.272

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		-0.18
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: rs1541010; hg19: chr10-13755544;