14-51489516-A-G

Position:

• chr14-51489516-A-G

Variant summary

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

The ENST00000356218.8(FRMD6):​c.-210+96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,522 control chromosomes in the GnomAD database, including 344 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 0.049 (344 hom., cov: 33)
  • Exomes 𝑓: 0.022 (0 hom.)
• Consequence: FRMD6 ENST00000356218.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD6-AS2	NR_051990.1	n.245-34701T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD6-AS2	ENST00000697567.1	n.264+94650T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7407 AN: 152174 Hom.: 332 Cov.: 33

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.0217 AC: 5 AN: 230 Hom.: 0 AF XY: 0.0270 AC XY: 4 AN XY: 148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.0225

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0490 AC: 7465 AN: 152292 Hom.: 344 Cov.: 33 AF XY: 0.0533 AC XY: 3966 AN XY: 74478

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.0913

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0321

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0217 Hom.: 121

Bravo AF: 0.0556

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.68

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: rs10484092; hg19: chr14-51956234;