rs472197

Positions:

• chr12-69532924-G-A
• chr12-69532924-G-C

Variant summary

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

The NM_001278356.2(FRS2):​c.-122+868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,986 control chromosomes in the GnomAD database, including 28,972 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 0.60 (28972 hom., cov: 32)
• Consequence: FRS2 NM_001278356.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRS2	NM_001278356.2	c.-122+868G>A		intron_variant		ENST00000549921.6	NP_001265285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRS2	ENST00000549921.6	c.-122+868G>A		intron_variant		1	NM_001278356.2	ENSP00000450048	P1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91024 AN: 151868 Hom.: 28926 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.600 AC: 91138 AN: 151986 Hom.: 28972 Cov.: 32 AF XY: 0.595 AC XY: 44172 AN XY: 74264

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.578

Alfa AF: 0.540 Hom.: 10536

Bravo AF: 0.614

Asia WGS AF: 0.626 AC: 2176 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.070
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs472197; hg19: chr12-69926704;