Genetic Variant FRMD6: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
FRMD6-AS1	NR_037676.1 link	n.571A>G	non_coding_transcript_exon_variant	Exon 1 of 1
FRMD6	XM_047430923.1 link	c.-486T>C	5_prime_UTR_variant	Exon 1 of 14	XP_047286879.1
FRMD6	XM_047430935.1 link	c.-486T>C	5_prime_UTR_variant	Exon 1 of 14	XP_047286891.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
FRMD6	ENST00000356218.8 link	c.-146-38517T>C	intron_variant	Intron 2 of 14	1	ENSP00000348550.4
FRMD6-AS2	ENST00000617151.1 link	n.571A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
FRMD6	ENST00000556137.5 link	n.509-38517T>C	intron_variant	Intron 3 of 3	4

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over