chr12-69532924-G-A

Variant names:

• chr12-69532924-G-A
• rs472197
• NM_001278356.2:c.-122+868G>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.-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
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 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.-122+868G>A		intron	N/A	NP_001265285.1
	FRS2	NM_001042555.3		c.-122+868G>A		intron	N/A	NP_001036020.1
	FRS2	NM_001278351.2		c.-190+868G>A		intron	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.-122+868G>A		intron	N/A	ENSP00000450048.1
	FRS2	ENST00000550389.5	TSL:1	c.-121-29256G>A		intron	N/A	ENSP00000447241.1
	FRS2	ENST00000550937.5	TSL:5	c.-247+868G>A		intron	N/A	ENSP00000447804.1

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

African (AFR) AF: 0.822 AC: 34110 AN: 41508

American (AMR) AF: 0.515 AC: 7856 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2060 AN: 3464

East Asian (EAS) AF: 0.635 AC: 3271 AN: 5150

South Asian (SAS) AF: 0.671 AC: 3232 AN: 4816

European-Finnish (FIN) AF: 0.441 AC: 4643 AN: 10520

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34232 AN: 67954

Other (OTH) AF: 0.578 AC: 1220 AN: 2112

Alfa AF: 0.541 Hom.: 11840

Bravo AF: 0.614

Asia WGS AF: 0.626 AC: 2176 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.070
DANN	Benign	0.70
PhyloP100		-1.6
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: rs472197; hg19: chr12-69926704;