ENST00000356218.8:c.-210+96A>G

Variant names:

• chr14-51489516-A-G
• rs10484092
• ENST00000356218.8:c.-210+96A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356218.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD6	NM_001042481.3		c.-210+96A>G		intron	N/A	NP_001035946.1
	FRMD6-AS2	NR_051990.1		n.245-34701T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD6	ENST00000356218.8	TSL:1	c.-210+96A>G		intron	N/A	ENSP00000348550.4
	FRMD6	ENST00000556137.5	TSL:4	n.321+96A>G		intron	N/A
	FRMD6-AS2	ENST00000556617.5	TSL:4	n.245-34701T>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0225 AC: 5 AN: 222

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0854 AC: 3548 AN: 41544

American (AMR) AF: 0.0913 AC: 1396 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3468

East Asian (EAS) AF: 0.168 AC: 870 AN: 5188

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4826

European-Finnish (FIN) AF: 0.0321 AC: 341 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0128 AC: 874 AN: 68032

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0294 Hom.: 492

Bravo AF: 0.0556

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		0.061
PromoterAI		0.070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10484092; hg19: chr14-51956234;