rs17586545

Variant names:

• chr14-51568300-C-T
• rs17586545
• ENST00000356218.8:c.-209-2048C>T

Variant summary

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

The ENST00000356218.8(FRMD6):​c.-209-2048C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 152,318 control chromosomes in the GnomAD database, including 151 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 0.039 (151 hom., cov: 33)
• Consequence: FRMD6 ENST00000356218.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356218.8. 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
	FRMD6	NM_001042481.3		c.-209-2048C>T		intron	N/A	NP_001035946.1
	FRMD6-AS2	NR_047477.2		n.244+15866G>A		intron	N/A
	FRMD6-AS2	NR_051990.1		n.244+15866G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD6	ENST00000356218.8	TSL:1	c.-209-2048C>T		intron	N/A	ENSP00000348550.4
	FRMD6	ENST00000554745.1	TSL:4	n.215-2048C>T		intron	N/A
	FRMD6	ENST00000555952.5	TSL:2	n.147-2048C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5939 AN: 152202 Hom.: 151 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0390 AC: 5942 AN: 152318 Hom.: 151 Cov.: 33 AF XY: 0.0388 AC XY: 2887 AN XY: 74474

African (AFR) AF: 0.0140 AC: 581 AN: 41584

American (AMR) AF: 0.0394 AC: 603 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3472

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5178

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4822

European-Finnish (FIN) AF: 0.0594 AC: 630 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0542 AC: 3685 AN: 68030

Other (OTH) AF: 0.0336 AC: 71 AN: 2116

Alfa AF: 0.0515 Hom.: 135

Bravo AF: 0.0369

Asia WGS AF: 0.0180 AC: 63 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	0.39
DANN	Benign	0.62
PhyloP100		-1.2
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: rs17586545; hg19: chr14-52035018;