rs34003

Variant names:

• chr5-142595502-A-C
• rs34003
• NM_000800.5:c.274-18T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-142595502-A-C
• chr5-142595502-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000800.5(FGF1):​c.274-18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,605,964 control chromosomes in the GnomAD database, including 181,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.53 (22746 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158687 hom.)
• Consequence: FGF1 NM_000800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF1	NM_000800.5	MANE Select	c.274-18T>G		intron	N/A	NP_000791.1
	FGF1	NM_001144892.3		c.274-18T>G		intron	N/A	NP_001138364.1
	FGF1	NM_001144934.2		c.274-18T>G		intron	N/A	NP_001138406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF1	ENST00000337706.7	TSL:2 MANE Select	c.274-18T>G		intron	N/A	ENSP00000338548.2
	FGF1	ENST00000359370.10	TSL:1	c.274-18T>G		intron	N/A	ENSP00000352329.6
	FGF1	ENST00000612258.4	TSL:1	c.274-18T>G		intron	N/A	ENSP00000479024.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80852 AN: 151882 Hom.: 22696 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.515

GnomAD2 exomes AF: 0.481 AC: 117529 AN: 244134 AF XY: 0.479

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.386

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.634

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.463 AC: 673165 AN: 1453964 Hom.: 158687 Cov.: 30 AF XY: 0.463 AC XY: 334957 AN XY: 723116

African (AFR) AF: 0.738 AC: 24486 AN: 33176

American (AMR) AF: 0.393 AC: 17273 AN: 43916

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 11733 AN: 25754

East Asian (EAS) AF: 0.655 AC: 25924 AN: 39594

South Asian (SAS) AF: 0.473 AC: 40418 AN: 85440

European-Finnish (FIN) AF: 0.487 AC: 25887 AN: 53144

Middle Eastern (MID) AF: 0.522 AC: 2987 AN: 5720

European-Non Finnish (NFE) AF: 0.448 AC: 495756 AN: 1107154

Other (OTH) AF: 0.478 AC: 28701 AN: 60066

GnomAD4 genome AF: 0.533 AC: 80963 AN: 152000 Hom.: 22746 Cov.: 32 AF XY: 0.532 AC XY: 39501 AN XY: 74282

African (AFR) AF: 0.719 AC: 29832 AN: 41464

American (AMR) AF: 0.423 AC: 6465 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3260 AN: 5152

South Asian (SAS) AF: 0.485 AC: 2332 AN: 4812

European-Finnish (FIN) AF: 0.493 AC: 5206 AN: 10558

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30744 AN: 67954

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.469 Hom.: 43638

Bravo AF: 0.536

Asia WGS AF: 0.544 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
DANN	Benign	0.78
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34003; hg19: chr5-141975067; COSMIC: COSV61803641;