NM_018027.5:c.46-172290C>A

Variant names:

• chr10-14031202-G-T
• rs7901829
• NM_018027.5:c.46-172290C>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.46-172290C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 151,960 control chromosomes in the GnomAD database, including 50,853 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 0.81 (50853 hom., cov: 31)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018027.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	NM_018027.5	MANE Select	c.46-172290C>A		intron	N/A	NP_060497.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	ENST00000357447.7	TSL:1 MANE Select	c.46-172290C>A		intron	N/A	ENSP00000350032.2	Q9P2Q2
	FRMD4A	ENST00000495956.3	TSL:2	c.46-172290C>A		intron	N/A	ENSP00000488764.2	A0A0J9YYA7
	FRMD4A	ENST00000649423.1		c.33+142810C>A		intron	N/A	ENSP00000497182.1	A0A3B3IS86

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123784 AN: 151842 Hom.: 50833 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.815 AC: 123846 AN: 151960 Hom.: 50853 Cov.: 31 AF XY: 0.814 AC XY: 60434 AN XY: 74252

African (AFR) AF: 0.711 AC: 29434 AN: 41386

American (AMR) AF: 0.830 AC: 12673 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2878 AN: 3472

East Asian (EAS) AF: 0.927 AC: 4786 AN: 5164

South Asian (SAS) AF: 0.927 AC: 4470 AN: 4820

European-Finnish (FIN) AF: 0.815 AC: 8577 AN: 10526

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58183 AN: 68014

Other (OTH) AF: 0.825 AC: 1743 AN: 2112

Alfa AF: 0.837 Hom.: 99239

Bravo AF: 0.809

Asia WGS AF: 0.915 AC: 3181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7901829; hg19: chr10-14073201;