5-142698298-T-C

Variant names:

• chr5-142698298-T-C
• rs1860230
• ENST00000510311.6:n.761-14503T>C

Variant summary

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

The ENST00000510311.6(SPRY4-AS1):​n.761-14503T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,192 control chromosomes in the GnomAD database, including 15,617 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (15617 hom., cov: 32)
• Consequence: SPRY4-AS1 ENST00000510311.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678
• Publications: 8 publications found

Genes affected

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

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510311.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF1	NM_001257205.1		c.-711A>G		upstream_gene	N/A	NP_001244134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRY4-AS1	ENST00000510311.6	TSL:4	n.761-14503T>C		intron	N/A
	SPRY4-AS1	ENST00000655828.2		n.420-5083T>C		intron	N/A
	SPRY4-AS1	ENST00000660053.2		n.52-14503T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50216 AN: 152074 Hom.: 15554 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50337 AN: 152192 Hom.: 15617 Cov.: 32 AF XY: 0.331 AC XY: 24648 AN XY: 74416

African (AFR) AF: 0.812 AC: 33703 AN: 41512

American (AMR) AF: 0.262 AC: 4004 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3468

East Asian (EAS) AF: 0.424 AC: 2185 AN: 5156

South Asian (SAS) AF: 0.298 AC: 1439 AN: 4828

European-Finnish (FIN) AF: 0.108 AC: 1142 AN: 10608

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.0972 AC: 6611 AN: 68022

Other (OTH) AF: 0.295 AC: 624 AN: 2112

Alfa AF: 0.171 Hom.: 14338

Bravo AF: 0.365

Asia WGS AF: 0.396 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.4
DANN	Benign	0.55
PhyloP100		0.68
PromoterAI		0.0084	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1860230; hg19: chr5-142077863;