14-51475406-C-T

Variant names:

• chr14-51475406-C-T
• rs17123958
• XM_047430921.1:c.-289-13935C>T

Variant summary

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

The XM_047430921.1(FRMD6):​c.-289-13935C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,200 control chromosomes in the GnomAD database, including 938 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 0.088 (938 hom., cov: 32)
• Consequence: FRMD6 XM_047430921.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD6	XM_047430921.1	c.-289-13935C>T		intron_variant	Intron 2 of 16		XP_047286877.1
FRMD6	XM_047430922.1	c.-289-13935C>T		intron_variant	Intron 2 of 16		XP_047286878.1
FRMD6	XM_047430926.1	c.-392-13935C>T		intron_variant	Intron 2 of 17		XP_047286882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD6-AS2	ENST00000556617.5	n.245-20591G>A		intron_variant	Intron 2 of 2	4
FRMD6-AS2	ENST00000697566.1	n.119-82357G>A		intron_variant	Intron 1 of 4
FRMD6-AS2	ENST00000697567.1	n.265-82357G>A		intron_variant	Intron 2 of 3
FRMD6-AS2	ENST00000697568.1	n.260-78286G>A		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13395 AN: 152082 Hom.: 928 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0882 AC: 13429 AN: 152200 Hom.: 938 Cov.: 32 AF XY: 0.0892 AC XY: 6640 AN XY: 74402

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0451

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0604 Hom.: 579

Bravo AF: 0.106

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17123958; hg19: chr14-51942124;