5-142614066-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07

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]

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

ACMG classification

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 GnomAd at 530 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF1	NM_000800.5	c.62G>A	p.Gly21Glu	missense_variant	2/4	ENST00000337706.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 530 AN: 152158 Hom.: 8 Cov.: 33

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.: 5 AF XY: 0.00522 AC XY: 710 AN XY: 135906

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.: 31 Cov.: 31 AF XY: 0.00435 AC XY: 3161 AN XY: 727238

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.: 8 Cov.: 33 AF XY: 0.00356 AC XY: 265 AN XY: 74456

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.: 5

Bravo AF: 0.00349

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00442 AC: 537

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00518

EpiControl AF: 0.00616

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	15
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	D
MetaRNN	Benign	0.0075	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
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	T
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	T
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

Other links and lift over

dbSNP: rs17223632; hg19: chr5-141993631; COSMIC: COSV61804752;