chr5-142614066-C-T

Position:

chr5-142614066-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000800.5(FGF1):c.62G>A(p.Gly21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,614,152 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0035 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 31 hom. )

Consequence

FGF1
NM_000800.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

FGF1 (HGNC:3665): (fibroblast growth factor 1) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

FGF1 links:

SPRY4-AS1 (HGNC:53465): (SPRY4 antisense RNA 1)

SPRY4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007540971).

BP6

Variant 5-142614066-C-T is Benign according to our data. Variant chr5-142614066-C-T is described in ClinVar as [Benign]. Clinvar id is 786817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00399 (5833/1461876) while in subpopulation MID AF= 0.0182 (105/5766). AF 95% confidence interval is 0.0154. There are 31 homozygotes in gnomad4_exome. There are 3161 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 529 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF1	NM_000800.5 linkuse as main transcript	c.62G>A	p.Gly21Glu	missense_variant	2/4	ENST00000337706.7	NP_000791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF1	ENST00000337706.7 linkuse as main transcript	c.62G>A	p.Gly21Glu	missense_variant	2/4	2	NM_000800.5	ENSP00000338548	P1	P05230-1
SPRY4-AS1	ENST00000443800.5 linkuse as main transcript	n.356+32152C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

530

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00404

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00452

AC:

1136

AN:

251470

Hom.:

AF XY:

0.00522

AC XY:

710

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00734

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00399

AC:

5833

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

3161

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00945

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.00358

Gnomad4 OTH exome

AF:

0.00495

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152276

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00404

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00440

Hom.:

Bravo

AF:

0.00349

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00442

AC:

537

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00616

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.58

D;D;D;D;D;D;D;.;T;D;D;.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.76

.;.;.;T;.;.;.;T;T;.;.;T;T

MetaRNN

Benign

0.0075

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L;L;L;L;L;L;.;L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.3

N;.;.;.;.;N;N;D;D;N;N;D;D

REVEL

Benign

0.037

Sift

Benign

0.066

T;.;.;.;.;T;T;D;D;T;T;T;T

Sift4G

Benign

0.42

T;T;T;T;T;T;T;T;T;T;T;.;T

Polyphen

0.066

B;B;B;B;B;B;B;B;.;B;B;.;.

Vest4

0.17

MVP

0.49

MPC

0.25

ClinPred

0.0082

GERP RS

1.9

Varity_R

0.19

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over