rs10484090

Variant names:

• chr14-51533315-A-G
• rs10484090
• ENST00000356218.8:c.-209-37033A>G

Variant summary

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

The ENST00000356218.8(FRMD6):​c.-209-37033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,292 control chromosomes in the GnomAD database, including 103 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 0.030 (103 hom., cov: 32)
• Consequence: FRMD6 ENST00000356218.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 1 publications found

Genes affected

FRMD6 (HGNC:19839): (FERM domain containing 6) Predicted to be involved in actomyosin structure organization. Predicted to act upstream of or within apical constriction; cellular protein localization; and regulation of actin filament-based process. Predicted to be located in apical junction complex. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

FRMD6-AS2 (HGNC:43637): (FRMD6 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD6	NM_001042481.3	c.-209-37033A>G		intron_variant	Intron 1 of 14		NP_001035946.1
FRMD6-AS2	NR_051990.1	n.244+50851T>C		intron_variant	Intron 2 of 2
FRMD6	XM_011536424.2	c.-209-37033A>G		intron_variant	Intron 2 of 15		XP_011534726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD6	ENST00000356218.8	c.-209-37033A>G		intron_variant	Intron 1 of 14	1		ENSP00000348550.4
FRMD6	ENST00000556137.5	n.446-37033A>G		intron_variant	Intron 2 of 3	4
FRMD6-AS2	ENST00000556617.5	n.244+50851T>C		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4608 AN: 152174 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0287

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0291

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

GnomAD4 genome AF: 0.0303 AC: 4612 AN: 152292 Hom.: 103 Cov.: 32 AF XY: 0.0299 AC XY: 2226 AN XY: 74442

African (AFR) AF: 0.0576 AC: 2394 AN: 41564

American (AMR) AF: 0.0205 AC: 313 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 71 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0287 AC: 138 AN: 4812

European-Finnish (FIN) AF: 0.0186 AC: 198 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0208 AC: 1412 AN: 68028

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0243 Hom.: 82

Bravo AF: 0.0307

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.8
DANN	Benign	0.87
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism

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: rs10484090; hg19: chr14-52000033;