Genetic Variant ENST00000356218.8:c.-146-38517T>C (chr14-51651174-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000356218.8(FRMD6):c.-146-38517T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,348 control chromosomes in the GnomAD database, including 44,003 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 0.76 ( 43933 hom., cov: 32)

Exomes 𝑓: 0.81 ( 70 hom. )

Consequence

FRMD6
ENST00000356218.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0880

Publications

11 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:

FRMD6-AS1 (HGNC:20129): (FRMD6 antisense RNA 1)

FRMD6-AS1 links:

Genome browser will be placed here

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=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD6	NM_001042481.3		c.-146-38517T>C		intron	N/A	NP_001035946.1
	FRMD6-AS1	NR_037676.1		n.571A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FRMD6	ENST00000356218.8	TSL:1	c.-146-38517T>C	intron	N/A	ENSP00000348550.4
FRMD6-AS2	ENST00000617151.1	TSL:6	n.571A>G	non_coding_transcript_exon	Exon 1 of 1
FRMD6	ENST00000556137.5	TSL:4	n.509-38517T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

115038

AN:

152014

Hom.:

43885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.703

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.772

GnomAD4 exome

AF:

0.810

AC:

175

AN:

216

Hom.:

Cov.:

AF XY:

0.792

AC XY:

133

AN XY:

168

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.798

AC:

142

AN:

178

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.757

AC:

115146

AN:

152132

Hom.:

43933

Cov.:

AF XY:

0.753

AC XY:

56004

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.732

AC:

30407

AN:

41518

American (AMR)

AF:

0.786

AC:

12013

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

2522

AN:

3472

East Asian (EAS)

AF:

0.415

AC:

2136

AN:

5148

South Asian (SAS)

AF:

0.703

AC:

3385

AN:

4818

European-Finnish (FIN)

AF:

0.735

AC:

7794

AN:

10602

Middle Eastern (MID)

AF:

0.782

AC:

230

AN:

294

European-Non Finnish (NFE)

AF:

0.798

AC:

54278

AN:

67976

Other (OTH)

AF:

0.775

AC:

1635

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1412

2823

4235

5646

7058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.786

Hom.:

107258

Bravo

AF:

0.757

Asia WGS

AF:

0.622

AC:

2163

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.4

(source)

DANN

Benign

0.85

PhyloP100

0.088

Mutation Taster

=100/0

polymorphism (auto)

(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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over