rs11259096

Positions:

• chr10-14436619-T-C
• chr10-14436619-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475141.2(FRMD4A):​c.-305+25449A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 514,240 control chromosomes in the GnomAD database, including 2,264 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 0.10 (1413 hom., cov: 31)
  • Exomes 𝑓: 0.054 (851 hom.)
• Consequence: FRMD4A ENST00000475141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.688

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]

MIR1265 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR1265	NR_031668.1	n.44T>C		non_coding_transcript_exon_variant	1/1
MIR1265	unassigned_transcript_1724	n.*9T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000475141.2	c.-305+25449A>G		intron_variant		1		ENSP00000473870.1
FRMD4A	ENST00000493380.5	c.-82+25449A>G		intron_variant		1		ENSP00000474863.1
MIR1265	ENST00000408444.1	n.44T>C		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15787 AN: 152020 Hom.: 1409 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0790

GnomAD3 exomes AF: 0.0579 AC: 12488 AN: 215620 Hom.: 692 AF XY: 0.0571 AC XY: 6640 AN XY: 116348

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.0336

Gnomad ASJ exome AF: 0.0541

Gnomad EAS exome AF: 0.000297

Gnomad SAS exome AF: 0.0633

Gnomad FIN exome AF: 0.0392

Gnomad NFE exome AF: 0.0514

Gnomad OTH exome AF: 0.0560

GnomAD4 exome AF: 0.0544 AC: 19690 AN: 362102 Hom.: 851 Cov.: 0 AF XY: 0.0544 AC XY: 11171 AN XY: 205368

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.0543

Gnomad4 EAS exome AF: 0.000311

Gnomad4 SAS exome AF: 0.0629

Gnomad4 FIN exome AF: 0.0389

Gnomad4 NFE exome AF: 0.0494

Gnomad4 OTH exome AF: 0.0595

GnomAD4 genome AF: 0.104 AC: 15811 AN: 152138 Hom.: 1413 Cov.: 31 AF XY: 0.102 AC XY: 7555 AN XY: 74376

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.0604

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0571

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0496

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0679 Hom.: 769

Bravo AF: 0.112

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11259096; hg19: chr10-14478618;