NM_018027.5:c.206+5858T>A

Variant names:

• chr10-13804956-A-T
• rs11258628
• NM_018027.5:c.206+5858T>A

Variant summary

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

The NM_018027.5(FRMD4A):​c.206+5858T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 152,212 control chromosomes in the GnomAD database, including 168 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 0.039 (168 hom., cov: 31)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.206+5858T>A		intron_variant	Intron 4 of 24	ENST00000357447.7	NP_060497.3
FRMD4A	NM_001318337.2	c.305+5858T>A		intron_variant	Intron 3 of 23		NP_001305266.1
FRMD4A	NM_001318336.2	c.254+5858T>A		intron_variant	Intron 3 of 23		NP_001305265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.206+5858T>A		intron_variant	Intron 4 of 24	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5937 AN: 152094 Hom.: 168 Cov.: 31

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0390 AC: 5935 AN: 152212 Hom.: 168 Cov.: 31 AF XY: 0.0378 AC XY: 2814 AN XY: 74412

African (AFR) AF: 0.00935 AC: 388 AN: 41516

American (AMR) AF: 0.0401 AC: 614 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4828

European-Finnish (FIN) AF: 0.0439 AC: 465 AN: 10594

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0574 AC: 3901 AN: 68002

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

Alfa AF: 0.0494 Hom.: 26

Bravo AF: 0.0373

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
DANN	Benign	0.83
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11258628; hg19: chr10-13846956;