dbSNP rs61737524: FRMD4B:p.Pro576Pro (chr3-69189939-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015123.3(FRMD4B):c.1728C>T(p.Pro576Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,592,604 control chromosomes in the GnomAD database, including 307 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 0.025 ( 176 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 131 hom. )

Consequence

FRMD4B
NM_015123.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=0.145 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4B	NM_015123.3 link	c.1728C>T	p.Pro576Pro	synonymous_variant	Exon 18 of 23	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8 link	c.1728C>T	p.Pro576Pro	synonymous_variant	Exon 18 of 23	1	NM_015123.3	ENSP00000381549.3
FRMD4B	ENST00000478263.5 link	c.684C>T	p.Pro228Pro	synonymous_variant	Exon 8 of 13	1		ENSP00000418682.1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3782

AN:

152114

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00602

AC:

1498

AN:

249008

AF XY:

0.00466

show subpopulations

Gnomad AFR exome

AF:

0.0871

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00247

AC:

3558

AN:

1440372

Hom.:

131

Cov.:

AF XY:

0.00206

AC XY:

1479

AN XY:

717990

show subpopulations

African (AFR)

AF:

0.0881

AC:

2903

AN:

32958

American (AMR)

AF:

0.00347

AC:

155

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25982

East Asian (EAS)

AF:

0.00

AC:

AN:

39506

South Asian (SAS)

AF:

0.000210

AC:

AN:

85636

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00262

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.000141

AC:

154

AN:

1092904

Other (OTH)

AF:

0.00521

AC:

311

AN:

59638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

141

282

422

563

704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.0249

AC:

3791

AN:

152232

Hom.:

176

Cov.:

AF XY:

0.0241

AC XY:

1792

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0873

AC:

3623

AN:

41514

American (AMR)

AF:

0.00785

AC:

120

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68032

Other (OTH)

AF:

0.0147

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

170

340

509

679

849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0110

Hom.:

Bravo

AF:

0.0283

Asia WGS

AF:

0.00462

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.2

(source)

DANN

Benign

0.57

PhyloP100

0.14

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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