14-51453104-A-G

Variant names:

• chr14-51453104-A-G
• rs7153703
• ENST00000697566.1:n.119-60055T>C

Variant summary

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

The ENST00000697566.1(FRMD6-AS2):​n.119-60055T>C 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-AS2 ENST00000697566.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713
• 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=-0.85).
• 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 rank	MANE	Protein	UniProt
FRMD6	XM_047430921.1	c.-290+20642A>G		intron_variant	Intron 2 of 16		XP_047286877.1
FRMD6	XM_047430922.1	c.-290+20611A>G		intron_variant	Intron 2 of 16		XP_047286878.1
FRMD6	XM_047430926.1	c.-393+20642A>G		intron_variant	Intron 2 of 17		XP_047286882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD6-AS2	ENST00000697566.1	n.119-60055T>C		intron_variant	Intron 1 of 4
FRMD6-AS2	ENST00000697567.1	n.265-60055T>C		intron_variant	Intron 2 of 3
FRMD6-AS2	ENST00000697568.1	n.260-55984T>C		intron_variant	Intron 2 of 5

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

African (AFR) AF: 0.315 AC: 13029 AN: 41398

American (AMR) AF: 0.227 AC: 3470 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3466

East Asian (EAS) AF: 0.153 AC: 791 AN: 5172

South Asian (SAS) AF: 0.303 AC: 1456 AN: 4804

European-Finnish (FIN) AF: 0.254 AC: 2669 AN: 10514

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13899 AN: 67954

Other (OTH) AF: 0.228 AC: 479 AN: 2102

Alfa AF: 0.208 Hom.: 11908

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
PhyloP100		0.71

Splicing

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

Other links and lift over

dbSNP: rs7153703; hg19: chr14-51919822;