Genetic Variant FRS3:c.-167-75T>C (chr6-41778251-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006653.5(FRS3):c.-167-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,126 control chromosomes in the GnomAD database, including 27,971 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 0.60 ( 27955 hom., cov: 32)

Exomes 𝑓: 0.57 ( 16 hom. )

Consequence

FRS3
NM_006653.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.427

Publications

6 publications found

Variant links:

Genes affected

FRS3 (HGNC:16970): (fibroblast growth factor receptor substrate 3) This gene encodes a substrate for the fibroblast growth factor receptor. The encoded protein is found in the peripheral plasma membrane and links fibroblast growth factor receptor stimulation to activators of Ras. The encoded protein down-regulates extracellular regulated kinase 2 through direct binding. [provided by RefSeq, Jul 2013]

FRS3 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FRS3	NM_006653.5 link	c.-167-75T>C	intron_variant	Intron 1 of 6	ENST00000373018.7	NP_006644.1	O43559A0A140VJJ7
FRS3	XM_011514254.2 link	c.-167-75T>C	intron_variant	Intron 1 of 6		XP_011512556.1	O43559A0A140VJJ7
FRS3	XM_047418097.1 link	c.-167-75T>C	intron_variant	Intron 2 of 7		XP_047274053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRS3	ENST00000373018.7 link	c.-167-75T>C		intron_variant	Intron 1 of 6	3	NM_006653.5	ENSP00000362109.3		O43559

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91143

AN:

151904

Hom.:

27904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.655

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.596

GnomAD4 exome

AF:

0.567

AC:

AN:

104

Hom.:

AF XY:

0.547

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.524

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.688

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

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:

0.600

AC:

91254

AN:

152022

Hom.:

27955

Cov.:

AF XY:

0.599

AC XY:

44530

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.713

AC:

29551

AN:

41466

American (AMR)

AF:

0.671

AC:

10258

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

1871

AN:

3470

East Asian (EAS)

AF:

0.534

AC:

2758

AN:

5168

South Asian (SAS)

AF:

0.655

AC:

3163

AN:

4828

European-Finnish (FIN)

AF:

0.508

AC:

5373

AN:

10572

Middle Eastern (MID)

AF:

0.534

AC:

156

AN:

292

European-Non Finnish (NFE)

AF:

0.536

AC:

36424

AN:

67924

Other (OTH)

AF:

0.595

AC:

1256

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1838

3676

5514

7352

9190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.560

Hom.:

85827

Bravo

AF:

0.618

Asia WGS

AF:

0.610

AC:

2124

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

(source)

DANN

Benign

0.86

PhyloP100

-0.43

PromoterAI

-0.027

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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