NM_018027.5:c.465-446T>C

Variant names:

• chr10-13748265-A-G
• rs10906466
• NM_018027.5:c.465-446T>C

Variant summary

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

The NM_018027.5(FRMD4A):​c.465-446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,120 control chromosomes in the GnomAD database, including 38,425 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 0.71 (38425 hom., cov: 32)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 9 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-AS1 (HGNC:56672): (FRMD4A antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	NM_018027.5	MANE Select	c.465-446T>C		intron	N/A	NP_060497.3
	FRMD4A	NM_001318337.2		c.564-446T>C		intron	N/A	NP_001305266.1
	FRMD4A	NM_001318336.2		c.513-446T>C		intron	N/A	NP_001305265.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	ENST00000357447.7	TSL:1 MANE Select	c.465-446T>C		intron	N/A	ENSP00000350032.2
	FRMD4A	ENST00000495956.3	TSL:2	c.465-446T>C		intron	N/A	ENSP00000488764.2
	FRMD4A	ENST00000264546.10	TSL:2	c.564-446T>C		intron	N/A	ENSP00000264546.6

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107241 AN: 152002 Hom.: 38406 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.705 AC: 107317 AN: 152120 Hom.: 38425 Cov.: 32 AF XY: 0.704 AC XY: 52313 AN XY: 74358

African (AFR) AF: 0.764 AC: 31714 AN: 41494

American (AMR) AF: 0.614 AC: 9384 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2588 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2394 AN: 5164

South Asian (SAS) AF: 0.560 AC: 2696 AN: 4812

European-Finnish (FIN) AF: 0.775 AC: 8209 AN: 10596

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47860 AN: 67974

Other (OTH) AF: 0.701 AC: 1480 AN: 2112

Alfa AF: 0.691 Hom.: 61314

Bravo AF: 0.699

Asia WGS AF: 0.561 AC: 1951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.078
DANN	Benign	0.24
PhyloP100		-1.3
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: rs10906466; hg19: chr10-13790265;