10-14031202-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4A	NM_018027.5	c.46-172290C>A		intron_variant		ENST00000357447.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4A	ENST00000357447.7	c.46-172290C>A		intron_variant		1	NM_018027.5	P2
FRMD4A	ENST00000495956.3	c.46-172290C>A		intron_variant		2		A2
FRMD4A	ENST00000648761.1	c.-128-6655C>A		intron_variant
FRMD4A	ENST00000649423.1	c.33+142810C>A		intron_variant

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

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.825

Alfa AF: 0.845 Hom.: 25846

Bravo AF: 0.809

Asia WGS AF: 0.915 AC: 3181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.30
Dann	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs7901829; hg19: chr10-14073201;