rs477028

Variant names:

• chr12-69580023-G-A
• rs477028
• NM_001278356.2:c.*5068G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-69580023-G-A
• chr12-69580023-G-T

Variant summary

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

The NM_001278356.2(FRS2):​c.*5068G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 152,238 control chromosomes in the GnomAD database, including 878 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 0.093 (878 hom., cov: 32)
• Consequence: FRS2 NM_001278356.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

FRS2 (HGNC:16971): (fibroblast growth factor receptor substrate 2) Enables fibroblast growth factor receptor binding activity and neurotrophin TRKA receptor binding activity. Involved in negative regulation of cardiac muscle cell differentiation. Acts upstream of or within fibroblast growth factor receptor signaling pathway. Located in adherens junction. Biomarker of renal cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRS2	NM_001278356.2	c.*5068G>A		downstream_gene_variant		ENST00000549921.6	NP_001265285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRS2	ENST00000549921.6	c.*5068G>A		downstream_gene_variant		1	NM_001278356.2	ENSP00000450048.1
FRS2	ENST00000550389.5	c.*5068G>A		downstream_gene_variant		1		ENSP00000447241.1
FRS2	ENST00000397997.6	c.*5068G>A		downstream_gene_variant		5		ENSP00000381083.2

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14188 AN: 152120 Hom.: 878 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0977

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

GnomAD4 genome AF: 0.0932 AC: 14187 AN: 152238 Hom.: 878 Cov.: 32 AF XY: 0.0892 AC XY: 6637 AN XY: 74424

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0967

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0967

Alfa AF: 0.0643 Hom.: 93

Bravo AF: 0.0892

Asia WGS AF: 0.0220 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs477028; hg19: chr12-69973803;