Genetic Variant FRMD6:c.-209-37033A>G (chr14-51533315-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001042481.3(FRMD6):c.-209-37033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,292 control chromosomes in the GnomAD database, including 103 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 0.030 ( 103 hom., cov: 32)

Consequence

FRMD6
NM_001042481.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0120

Publications

1 publications found

Variant links:

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 links:

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

FRMD6-AS2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001042481.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042481.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD6	NM_001042481.3		c.-209-37033A>G		intron	N/A	NP_001035946.1	Q96NE9-2
	FRMD6-AS2	NR_051990.1		n.244+50851T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRMD6	ENST00000356218.8	TSL:1	c.-209-37033A>G	intron	N/A	ENSP00000348550.4	Q96NE9-2
FRMD6	ENST00000556137.5	TSL:4	n.446-37033A>G	intron	N/A
FRMD6-AS2	ENST00000556617.5	TSL:4	n.244+50851T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4608

AN:

152174

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0205

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0287

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.0291

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

GnomAD4 genome

AF:

0.0303

AC:

4612

AN:

152292

Hom.:

103

Cov.:

AF XY:

0.0299

AC XY:

2226

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0576

AC:

2394

AN:

41564

American (AMR)

AF:

0.0205

AC:

313

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0287

AC:

138

AN:

4812

European-Finnish (FIN)

AF:

0.0186

AC:

198

AN:

10620

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0208

AC:

1412

AN:

68028

Other (OTH)

AF:

0.0288

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

228

456

684

912

1140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0307

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.8

(source)

DANN

Benign

0.87

PhyloP100

-0.012

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over