rs1541010

chr10-13713544-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105376426 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
FRMD4A	NM_018027.5	c.760-6431G>A		intron_variant		ENST00000357447.7
LOC105376426	XR_001747371.2	n.260+1530C>T		intron_variant, non_coding_transcript_variant
FRMD4A	NM_001318336.2	c.808-6431G>A		intron_variant
FRMD4A	NM_001318337.2	c.859-6431G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4A	ENST00000357447.7	c.760-6431G>A		intron_variant		1	NM_018027.5	P2
FRMD4A	ENST00000264546.10	c.859-6431G>A		intron_variant		2
FRMD4A	ENST00000495956.3	c.760-6431G>A		intron_variant		2		A2
FRMD4A	ENST00000342409.3	n.1189-6431G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.258

Alfa AF: 0.273 Hom.: 8557

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

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: rs1541010; hg19: chr10-13755544;