rs7095537

Positions:

• chr10-13754225-T-C

Variant summary

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

The NM_018027.5(FRMD4A):​c.465-6406A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,600 control chromosomes in the GnomAD database, including 2,431 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 0.17 (2431 hom., cov: 31)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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-AS1 (HGNC:56672): (FRMD4A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.465-6406A>G		intron_variant		ENST00000357447.7	NP_060497.3
FRMD4A	NM_001318336.2	c.513-6406A>G		intron_variant			NP_001305265.1
FRMD4A	NM_001318337.2	c.564-6406A>G		intron_variant			NP_001305266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.465-6406A>G		intron_variant		1	NM_018027.5	ENSP00000350032	P2
FRMD4A-AS1	ENST00000449462.1	n.310-1811T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26046 AN: 151482 Hom.: 2431 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.172 AC: 26048 AN: 151600 Hom.: 2431 Cov.: 31 AF XY: 0.170 AC XY: 12627 AN XY: 74108

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.0855

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.171

Alfa AF: 0.181 Hom.: 3161

Bravo AF: 0.178

Asia WGS AF: 0.248 AC: 859 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.61

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: rs7095537; hg19: chr10-13796225;