15-39618230-A-G

Position:

• chr15-39618230-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (14090 hom., cov: 32)
  • Exomes 𝑓: 0.30 (70140 hom.)
• Consequence: FSIP1 NM_152597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FSIP1	NM_152597.5	c.1204T>C	p.Cys402Arg	missense_variant	11/12	ENST00000350221.4	NP_689810.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSIP1	ENST00000350221.4	c.1204T>C	p.Cys402Arg	missense_variant	11/12	1	NM_152597.5	ENSP00000280236.3
FSIP1	ENST00000642527.1	n.13T>C		non_coding_transcript_exon_variant	1/4			ENSP00000496642.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60292 AN: 152028 Hom.: 14064 Cov.: 32

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

GnomAD3 exomes AF: 0.304 AC: 75150 AN: 247318 Hom.: 12758 AF XY: 0.302 AC XY: 40562 AN XY: 134424

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 SAS exome AF: 0.278

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.: 32 AF XY: 0.302 AC XY: 217193 AN XY: 719368

Gnomad4 AFR exome AF: 0.675

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.397 AC: 60364 AN: 152146 Hom.: 14090 Cov.: 32 AF XY: 0.391 AC XY: 29096 AN XY: 74376

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.370

Alfa AF: 0.310 Hom.: 19854

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	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.58
DEOGEN2	Benign	0.00081	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.070	T
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.0080
Sift	Benign	0.38	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.043
ClinPred		0.00058	T
GERP RS		-0.45
Varity_R		0.070
gMVP		0.010

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

LitVar

Other links and lift over

dbSNP: rs10152640; hg19: chr15-39910431; COSMIC: COSV63223450;