Genetic Variant FRMD4B:c.2985-1731A>C (chr3-69173712-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015123.3(FRMD4B):c.2985-1731A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,204 control chromosomes in the GnomAD database, including 61,505 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 0.89 ( 61505 hom., cov: 33)

Consequence

FRMD4B
NM_015123.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.229

Publications

5 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

new If you want to explore the variant's impact on the transcript NM_015123.3, 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4B	NM_015123.3	MANE Select	c.2985-1731A>C		intron	N/A	NP_055938.2	Q9Y2L6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRMD4B	ENST00000398540.8	TSL:1 MANE Select	c.2985-1731A>C	intron	N/A	ENSP00000381549.3	Q9Y2L6-1
FRMD4B	ENST00000478263.5	TSL:1	c.1941-1731A>C	intron	N/A	ENSP00000418682.1	E9PGA7
FRMD4B	ENST00000863518.1		c.2925-1731A>C	intron	N/A	ENSP00000533577.1

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134976

AN:

152086

Hom.:

61485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.956

Gnomad ASJ

AF:

0.992

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.821

Gnomad FIN

AF:

0.995

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.994

Gnomad OTH

AF:

0.913

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

GnomAD4 genome

AF:

0.887

AC:

135039

AN:

152204

Hom.:

61505

Cov.:

AF XY:

0.884

AC XY:

65766

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.682

AC:

28310

AN:

41494

American (AMR)

AF:

0.956

AC:

14622

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.992

AC:

3442

AN:

3470

East Asian (EAS)

AF:

0.656

AC:

3388

AN:

5168

South Asian (SAS)

AF:

0.820

AC:

3958

AN:

4824

European-Finnish (FIN)

AF:

0.995

AC:

10552

AN:

10608

Middle Eastern (MID)

AF:

0.952

AC:

280

AN:

294

European-Non Finnish (NFE)

AF:

0.994

AC:

67646

AN:

68034

Other (OTH)

AF:

0.913

AC:

1929

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

629

1259

1888

2518

3147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.955

Hom.:

195385

Bravo

AF:

0.876

Asia WGS

AF:

0.788

AC:

2740

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.8

(source)

DANN

Benign

0.64

PhyloP100

0.23

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

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