rs12885443

Positions:

• chr14-51608935-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042481.3(FRMD6):​c.-147+38525A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,144 control chromosomes in the GnomAD database, including 2,641 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 0.17 (2641 hom., cov: 32)
• Consequence: FRMD6 NM_001042481.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD6	NM_001042481.3	c.-147+38525A>C		intron_variant			NP_001035946.1
FRMD6	XM_011536424.2	c.-147+38525A>C		intron_variant			XP_011534726.1
FRMD6	XM_024449473.2	c.-146-80756A>C		intron_variant			XP_024305241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD6	ENST00000356218.8	c.-147+38525A>C		intron_variant		1		ENSP00000348550.4
FRMD6	ENST00000554745.1	n.278-34517A>C		intron_variant		4
FRMD6	ENST00000556137.5	n.508+38525A>C		intron_variant		4
FRMD6-AS2	ENST00000697569.1	n.23-24652T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26035 AN: 152026 Hom.: 2638 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.171 AC: 26054 AN: 152144 Hom.: 2641 Cov.: 32 AF XY: 0.173 AC XY: 12847 AN XY: 74366

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.166

Alfa AF: 0.204 Hom.: 4383

Bravo AF: 0.158

Asia WGS AF: 0.172 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.069
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs12885443; hg19: chr14-52075653;