ENST00000356218.8:c.-147+38525A>C

Variant names:

• chr14-51608935-A-C
• rs12885443
• ENST00000356218.8:c.-147+38525A>C

Variant summary

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

The ENST00000356218.8(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 ENST00000356218.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
FRMD6	NM_001042481.3	c.-147+38525A>C		intron_variant	Intron 2 of 14		NP_001035946.1
FRMD6	XM_011536424.2	c.-147+38525A>C		intron_variant	Intron 3 of 15		XP_011534726.1
FRMD6	XM_024449473.2	c.-146-80756A>C		intron_variant	Intron 1 of 13		XP_024305241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD6	ENST00000356218.8	c.-147+38525A>C		intron_variant	Intron 2 of 14	1		ENSP00000348550.4
FRMD6	ENST00000554745.1	n.278-34517A>C		intron_variant	Intron 2 of 2	4
FRMD6	ENST00000556137.5	n.508+38525A>C		intron_variant	Intron 3 of 3	4

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

African (AFR) AF: 0.0562 AC: 2332 AN: 41516

American (AMR) AF: 0.198 AC: 3029 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3470

East Asian (EAS) AF: 0.153 AC: 790 AN: 5168

South Asian (SAS) AF: 0.173 AC: 834 AN: 4820

European-Finnish (FIN) AF: 0.287 AC: 3034 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15110 AN: 67984

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.200 Hom.: 5373

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
PhyloP100		-2.1
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: rs12885443; hg19: chr14-52075653;