14-51453104-A-G

Position:

• chr14-51453104-A-G

Variant summary

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

The XM_047430921.1(FRMD6):​c.-290+20642A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,868 control chromosomes in the GnomAD database, including 4,776 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 0.24 (4776 hom., cov: 31)
• Consequence: FRMD6 XM_047430921.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD6	XM_047430921.1	c.-290+20642A>G		intron_variant			XP_047286877.1
FRMD6	XM_047430922.1	c.-290+20611A>G		intron_variant			XP_047286878.1
FRMD6	XM_047430926.1	c.-393+20642A>G		intron_variant			XP_047286882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD6-AS2	ENST00000697566.1	n.119-60055T>C		intron_variant
FRMD6-AS2	ENST00000697567.1	n.265-60055T>C		intron_variant
FRMD6-AS2	ENST00000697568.1	n.260-55984T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36865 AN: 151750 Hom.: 4782 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.243 AC: 36874 AN: 151868 Hom.: 4776 Cov.: 31 AF XY: 0.243 AC XY: 18018 AN XY: 74200

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.228

Alfa AF: 0.198 Hom.: 4582

Bravo AF: 0.243

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.9
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7153703; hg19: chr14-51919822;