10-14101637-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018027.5(FRMD4A):c.45+228421A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,966 control chromosomes in the GnomAD database, including 23,704 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 0.54 (23704 hom., cov: 31)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4A	NM_018027.5	c.45+228421A>C		intron_variant		ENST00000357447.7
FRMD4A	NR_134578.2	n.455-4499A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4A	ENST00000357447.7	c.45+228421A>C		intron_variant		1	NM_018027.5	P2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82132 AN: 151848 Hom.: 23707 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.541 AC: 82160 AN: 151966 Hom.: 23704 Cov.: 31 AF XY: 0.541 AC XY: 40203 AN XY: 74288

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.566

Alfa AF: 0.611 Hom.: 16616

Bravo AF: 0.515

Asia WGS AF: 0.580 AC: 2018 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.037
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs7921545; hg19: chr10-14143636;