ENST00000475141.2:c.-82+10838G>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475141.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	ENST00000475141.2	TSL:1	c.-82+10838G>T		intron	N/A	ENSP00000473870.1
	FRMD4A	ENST00000493380.5	TSL:1	c.-81-47660G>T		intron	N/A	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

African (AFR) AF: 0.868 AC: 36015 AN: 41504

American (AMR) AF: 0.968 AC: 14797 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 3278 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5168 AN: 5168

South Asian (SAS) AF: 0.965 AC: 4651 AN: 4822

European-Finnish (FIN) AF: 0.994 AC: 10542 AN: 10608

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66067 AN: 68022

Other (OTH) AF: 0.959 AC: 2026 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.41
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs586679; hg19: chr10-14419842;