chr10-13695029-C-A

Variant names:

• chr10-13695029-C-A
• rs4314962
• NM_018027.5:c.976-990G>T

Variant summary

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

The NM_018027.5(FRMD4A):​c.976-990G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,076 control chromosomes in the GnomAD database, including 44,398 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 0.74 (44398 hom., cov: 32)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4A	NM_018027.5	c.976-990G>T		intron_variant	Intron 14 of 24	ENST00000357447.7	NP_060497.3
FRMD4A	NM_001318337.2	c.1075-990G>T		intron_variant	Intron 13 of 23		NP_001305266.1
FRMD4A	NM_001318336.2	c.1024-990G>T		intron_variant	Intron 13 of 23		NP_001305265.1
FRMD4A	NM_001318338.2	c.49-990G>T		intron_variant	Intron 3 of 13		NP_001305267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4A	ENST00000357447.7	c.976-990G>T		intron_variant	Intron 14 of 24	1	NM_018027.5	ENSP00000350032.2

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113158 AN: 151958 Hom.: 44396 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.744 AC: 113202 AN: 152076 Hom.: 44398 Cov.: 32 AF XY: 0.750 AC XY: 55772 AN XY: 74330

African (AFR) AF: 0.467 AC: 19324 AN: 41406

American (AMR) AF: 0.820 AC: 12537 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2821 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4720 AN: 5184

South Asian (SAS) AF: 0.782 AC: 3771 AN: 4820

European-Finnish (FIN) AF: 0.887 AC: 9393 AN: 10590

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58033 AN: 68000

Other (OTH) AF: 0.770 AC: 1626 AN: 2112

Alfa AF: 0.792 Hom.: 91087

Bravo AF: 0.728

Asia WGS AF: 0.808 AC: 2807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.67
DANN	Benign	0.37
PhyloP100		-0.62
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: rs4314962; hg19: chr10-13737029;