rs2015015

Positions:

• chr10-13724692-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.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

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=-0.8).
• 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/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.759+13152C>T		intron_variant		ENST00000357447.7	NP_060497.3
LOC105376426	XR_001747371.2	n.261-445G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.759+13152C>T		intron_variant		1	NM_018027.5	ENSP00000350032	P2
FRMD4A	ENST00000264546.10	c.858+13152C>T		intron_variant		2		ENSP00000264546
FRMD4A	ENST00000495956.3	c.759+13152C>T		intron_variant		2		ENSP00000488764	A2
FRMD4A	ENST00000342409.3	n.1188+13152C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.366

Alfa AF: 0.347 Hom.: 12759

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

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: rs2015015; hg19: chr10-13766692;