dbSNP rs10152640: FSIP1:p.Cys402Arg (chr15-39618230-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_152597.5(FSIP1):c.1204T>C(p.Cys402Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,601,432 control chromosomes in the GnomAD database, including 84,230 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C402Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.40 ( 14090 hom., cov: 32)

Exomes 𝑓: 0.30 ( 70140 hom. )

Consequence

FSIP1
NM_152597.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Publications

26 publications found

Variant links:

Genes affected

FSIP1 (HGNC:21674): (fibrous sheath interacting protein 1)

FSIP1 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 (MetaRNN=2.7889657E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSIP1	NM_152597.5 link	c.1204T>C	p.Cys402Arg	missense_variant	Exon 11 of 12	ENST00000350221.4	NP_689810.3	Q8NA03A0A024R9J2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSIP1	ENST00000350221.4 link	c.1204T>C	p.Cys402Arg	missense_variant	Exon 11 of 12	1	NM_152597.5	ENSP00000280236.3		Q8NA03
FSIP1	ENST00000642527.1 link	n.13T>C		non_coding_transcript_exon_variant	Exon 1 of 4			ENSP00000496642.1		A0A2R8YHB5

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60292

AN:

152028

Hom.:

14064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.304

AC:

75150

AN:

247318

AF XY:

0.302

show subpopulations

Gnomad AFR exome

AF:

0.675

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.313

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.304

AC:

439938

AN:

1449286

Hom.:

70140

Cov.:

AF XY:

0.302

AC XY:

217193

AN XY:

719368

show subpopulations

African (AFR)

AF:

0.675

AC:

22412

AN:

33190

American (AMR)

AF:

0.205

AC:

9104

AN:

44466

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

7076

AN:

26016

East Asian (EAS)

AF:

0.366

AC:

14443

AN:

39434

South Asian (SAS)

AF:

0.278

AC:

23836

AN:

85762

European-Finnish (FIN)

AF:

0.310

AC:

16517

AN:

53254

Middle Eastern (MID)

AF:

0.330

AC:

1779

AN:

5388

European-Non Finnish (NFE)

AF:

0.295

AC:

325443

AN:

1101956

Other (OTH)

AF:

0.323

AC:

19328

AN:

59820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

13213

26426

39639

52852

66065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10938

21876

32814

43752

54690

<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:

0.397

AC:

60364

AN:

152146

Hom.:

14090

Cov.:

AF XY:

0.391

AC XY:

29096

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.661

AC:

27438

AN:

41494

American (AMR)

AF:

0.292

AC:

4462

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

946

AN:

3470

East Asian (EAS)

AF:

0.339

AC:

1761

AN:

5188

South Asian (SAS)

AF:

0.281

AC:

1356

AN:

4822

European-Finnish (FIN)

AF:

0.311

AC:

3286

AN:

10582

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.294

AC:

19989

AN:

67988

Other (OTH)

AF:

0.370

AC:

782

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1656

3312

4968

6624

8280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.322

Hom.:

40031

Bravo

AF:

0.407

TwinsUK

AF:

0.308

AC:

1141

ALSPAC

AF:

0.302

AC:

1163

ESP6500AA

AF:

0.639

AC:

2789

ESP6500EA

AF:

0.299

AC:

2544

ExAC

AF:

0.311

AC:

37673

Asia WGS

AF:

0.329

AC:

1149

AN:

3478

EpiCase

AF:

0.301

EpiControl

AF:

0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.5

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.00081

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.070

MetaRNN

Benign

0.0000028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PhyloP100

-0.042

PrimateAI

Benign

0.22

PROVEAN

Benign

0.30

REVEL

Benign

0.0080

Sift

Benign

0.38

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.0070

MPC

0.043

ClinPred

0.00058

GERP RS

-0.45

Varity_R

0.070

gMVP

0.010

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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