rs17586545

chr14-51568300-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD6-AS2	NR_051990.1	n.244+15866G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD6-AS2	ENST00000697567.1	n.264+15866G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0594

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0513 Hom.: 92

Bravo AF: 0.0369

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.39
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs17586545; hg19: chr14-52035018;