12-69580023-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278356.2. 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
	FRS2	NM_001278356.2	MANE Select	c.*5068G>A		downstream_gene	N/A	NP_001265285.1
	FRS2	NM_001042555.3		c.*5068G>A		downstream_gene	N/A	NP_001036020.1
	FRS2	NM_001278351.2		c.*5068G>A		downstream_gene	N/A	NP_001265280.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRS2	ENST00000549921.6	TSL:1 MANE Select	c.*5068G>A		downstream_gene	N/A	ENSP00000450048.1
	FRS2	ENST00000550389.5	TSL:1	c.*5068G>A		downstream_gene	N/A	ENSP00000447241.1
	FRS2	ENST00000397997.6	TSL:5	c.*5068G>A		downstream_gene	N/A	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

African (AFR) AF: 0.0248 AC: 1031 AN: 41550

American (AMR) AF: 0.0938 AC: 1435 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4830

European-Finnish (FIN) AF: 0.0967 AC: 1024 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9765 AN: 67998

Other (OTH) AF: 0.0967 AC: 204 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs477028; hg19: chr12-69973803;