rs586679

Variant names:

• chr10-14377843-C-A
• rs586679
• ENST00000475141.2:c.-82+10838G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-14377843-C-A
• chr10-14377843-C-G
• chr10-14377843-C-T

Variant summary

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

The ENST00000475141.2(FRMD4A):​c.-82+10838G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,208 control chromosomes in the GnomAD database, including 67,964 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 0.94 (67964 hom., cov: 30)
• Consequence: FRMD4A ENST00000475141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000475141.2	c.-82+10838G>T		intron_variant	Intron 2 of 3	1		ENSP00000473870.1
FRMD4A	ENST00000493380.5	c.-81-47660G>T		intron_variant	Intron 1 of 3	1		ENSP00000474863.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143585 AN: 152090 Hom.: 67933 Cov.: 30

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.965

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.944 AC: 143671 AN: 152208 Hom.: 67964 Cov.: 30 AF XY: 0.947 AC XY: 70509 AN XY: 74424

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.968

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.965

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.959

Alfa AF: 0.969 Hom.: 3353

Bravo AF: 0.938

Asia WGS AF: 0.977 AC: 3397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs586679; hg19: chr10-14419842;