chr10-14083636-A-T

Variant names:

• chr10-14083636-A-T
• rs922239
• ENST00000493380.5:c.*190T>A

Variant summary

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

The ENST00000493380.5(FRMD4A):​c.*190T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,156 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4173 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: FRMD4A ENST00000493380.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• 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

ENSG00000235410 (HGNC:58386):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000493380.5. 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.46-224724T>A		intron	N/A	NP_060497.3
	FRMD4A	NR_134578.2		n.761T>A		non_coding_transcript_exon	Exon 4 of 4
	FRMD4A-AS3	NR_120638.1		n.699+183A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	ENST00000493380.5	TSL:1	c.*190T>A		3_prime_UTR	Exon 4 of 4	ENSP00000474863.1
	FRMD4A	ENST00000357447.7	TSL:1 MANE Select	c.46-224724T>A		intron	N/A	ENSP00000350032.2
	ENSG00000235410	ENST00000451617.1	TSL:1	n.699+183A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34479 AN: 152010 Hom.: 4171 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.179 AC: 5 AN: 28 Hom.: 1 Cov.: 0 AF XY: 0.182 AC XY: 4 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.208 AC: 5 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.227 AC: 34499 AN: 152128 Hom.: 4173 Cov.: 33 AF XY: 0.231 AC XY: 17180 AN XY: 74366

African (AFR) AF: 0.152 AC: 6327 AN: 41508

American (AMR) AF: 0.287 AC: 4383 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3466

East Asian (EAS) AF: 0.377 AC: 1947 AN: 5158

South Asian (SAS) AF: 0.242 AC: 1166 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2515 AN: 10578

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16169 AN: 67984

Other (OTH) AF: 0.230 AC: 485 AN: 2108

Alfa AF: 0.222 Hom.: 461

Bravo AF: 0.227

Asia WGS AF: 0.289 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.59
PhyloP100		1.4
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: rs922239; hg19: chr10-14125635;