Genetic Variant NM_015123.3:c.708C>T (chr3-69221881-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_015123.3(FRMD4B):c.708C>T(p.Leu236Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 1,566,174 control chromosomes in the GnomAD database, including 8,387 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 0.079 ( 645 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7742 hom. )

Consequence

FRMD4B
NM_015123.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.822

Publications

8 publications found

Variant links:

Genes affected

FRMD4B (HGNC:24886): (FERM domain containing 4B) This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]

FRMD4B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=0.822 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015123.3. 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
	FRMD4B	NM_015123.3	MANE Select	c.708C>T	p.Leu236Leu	synonymous	Exon 9 of 23	NP_055938.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FRMD4B	ENST00000398540.8	TSL:1 MANE Select	c.708C>T	p.Leu236Leu	synonymous	Exon 9 of 23	ENSP00000381549.3
FRMD4B	ENST00000493880.5	TSL:4	c.381C>T	p.Leu127Leu	synonymous	Exon 6 of 8	ENSP00000418962.1
FRMD4B	ENST00000470070.6	TSL:5	n.602C>T		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes

AF:

0.0790

AC:

12017

AN:

152128

Hom.:

645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.0857

Gnomad AMR

AF:

0.0782

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0837

GnomAD2 exomes

AF:

0.0863

AC:

19629

AN:

227536

AF XY:

0.0891

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0564

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.000120

Gnomad FIN exome

AF:

0.0991

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.0971

GnomAD4 exome

AF:

0.0983

AC:

138966

AN:

1413928

Hom.:

7742

Cov.:

AF XY:

0.0976

AC XY:

68683

AN XY:

703832

show subpopulations

African (AFR)

AF:

0.0163

AC:

533

AN:

32796

American (AMR)

AF:

0.0605

AC:

2580

AN:

42634

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

4119

AN:

25532

East Asian (EAS)

AF:

0.000153

AC:

AN:

39288

South Asian (SAS)

AF:

0.0474

AC:

3922

AN:

82746

European-Finnish (FIN)

AF:

0.0988

AC:

5210

AN:

52710

Middle Eastern (MID)

AF:

0.109

AC:

622

AN:

5692

European-Non Finnish (NFE)

AF:

0.109

AC:

116734

AN:

1073676

Other (OTH)

AF:

0.0890

AC:

5240

AN:

58854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

5201

10403

15604

20806

26007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3958

7916

11874

15832

19790

<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:

0.0789

AC:

12011

AN:

152246

Hom.:

645

Cov.:

AF XY:

0.0780

AC XY:

5804

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0204

AC:

848

AN:

41560

American (AMR)

AF:

0.0781

AC:

1194

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

567

AN:

3468

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.0395

AC:

191

AN:

4830

European-Finnish (FIN)

AF:

0.101

AC:

1070

AN:

10580

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7853

AN:

68018

Other (OTH)

AF:

0.0829

AC:

175

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

566

1132

1699

2265

2831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0900

Hom.:

776

Bravo

AF:

0.0755

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.3

(source)

DANN

Benign

0.70

PhyloP100

0.82

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