rs7082219

Variant names:

• chr10-14333260-G-T
• rs7082219
• ENST00000475141.2:c.-81-3077C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475141.2(FRMD4A):​c.-81-3077C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,770 control chromosomes in the GnomAD database, including 5,501 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 0.26 (5501 hom., cov: 30)
• Consequence: FRMD4A ENST00000475141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 3 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 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.-81-3077C>A		intron_variant	Intron 2 of 3	1		ENSP00000473870.1
FRMD4A	ENST00000493380.5	c.-81-3077C>A		intron_variant	Intron 1 of 3	1		ENSP00000474863.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38889 AN: 151652 Hom.: 5506 Cov.: 30

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.256 AC: 38897 AN: 151770 Hom.: 5501 Cov.: 30 AF XY: 0.261 AC XY: 19327 AN XY: 74132

African (AFR) AF: 0.142 AC: 5866 AN: 41398

American (AMR) AF: 0.289 AC: 4414 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1119 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2112 AN: 5108

South Asian (SAS) AF: 0.295 AC: 1414 AN: 4796

European-Finnish (FIN) AF: 0.313 AC: 3292 AN: 10516

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19702 AN: 67914

Other (OTH) AF: 0.301 AC: 635 AN: 2108

Alfa AF: 0.280 Hom.: 23575

Bravo AF: 0.249

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.25
DANN	Benign	0.81
PhyloP100		-1.1
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: rs7082219; hg19: chr10-14375259;