14-51475406-C-T

Variant names:

• chr14-51475406-C-T
• rs17123958
• ENST00000556617.5:n.245-20591G>A

Variant summary

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

The ENST00000556617.5(FRMD6-AS2):​n.245-20591G>A 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-AS2 ENST00000556617.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 3 publications found

Genes affected

FRMD6-AS2 (HGNC:43637): (FRMD6 antisense RNA 2)

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]

ACMG classification

Our verdict: Benign. The variant received -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-AS2	NR_051990.1	n.245-20591G>A		intron_variant	Intron 2 of 2
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

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

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

African (AFR) AF: 0.144 AC: 5986 AN: 41498

American (AMR) AF: 0.196 AC: 2995 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3470

East Asian (EAS) AF: 0.101 AC: 525 AN: 5174

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4818

European-Finnish (FIN) AF: 0.0254 AC: 269 AN: 10602

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3066 AN: 68022

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0669 Hom.: 854

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
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs17123958; hg19: chr14-51942124;