10-13931579-C-T

Variant names:

• chr10-13931579-C-T
• rs7904694
• NM_018027.5:c.46-72667G>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.46-72667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,008 control chromosomes in the GnomAD database, including 1,410 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 0.11 (1410 hom., cov: 31)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.46-72667G>A		intron_variant	Intron 2 of 24	ENST00000357447.7	NP_060497.3
FRMD4A	NM_001318337.2	c.144+40077G>A		intron_variant	Intron 1 of 23		NP_001305266.1
FRMD4A	NM_001318336.2	c.94-72667G>A		intron_variant	Intron 1 of 23		NP_001305265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.46-72667G>A		intron_variant	Intron 2 of 24	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16979 AN: 151890 Hom.: 1412 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0907

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

GnomAD4 genome AF: 0.112 AC: 16999 AN: 152008 Hom.: 1410 Cov.: 31 AF XY: 0.113 AC XY: 8370 AN XY: 74300

African (AFR) AF: 0.203 AC: 8391 AN: 41436

American (AMR) AF: 0.110 AC: 1685 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1556 AN: 5142

South Asian (SAS) AF: 0.0796 AC: 383 AN: 4814

European-Finnish (FIN) AF: 0.0856 AC: 905 AN: 10570

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3297 AN: 67978

Other (OTH) AF: 0.0912 AC: 192 AN: 2106

Alfa AF: 0.0709 Hom.: 1120

Bravo AF: 0.120

Asia WGS AF: 0.196 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.36
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7904694; hg19: chr10-13973579;